| 1. |
- Salvadó, Gemma, et al.
(författare)
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The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
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| 2. |
- Berron, David, et al.
(författare)
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Medial temporal lobe connectivity and its associations with cognition in early Alzheimer's disease
- 2020
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:3, s. 1233-1248
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Tidskriftsartikel (refereegranskat)abstract
- Human episodic memory critically depends on subregions of the medial temporal lobe, which are part of functional brain systems such as the anterior-temporal and the posterior-medial system. Here we analysed how Alzheimer's pathology affects functional connectivity within these systems. Data from 256 amyloid-b-negative cognitively unimpaired, 103 amyloid-b-positive cognitively unimpaired, and 83 amyloid-b-positive individuals with mild cognitive impairment were analysed. Amyloid-b and tau pathology were measured using the CSF amyloid-b42/40 ratio and phosphorylated tau, respectively. We found that amyloid-b-positive cognitively unimpaired individuals were mainly characterized by decreased functional connectivity between the medial temporal lobe and regions in the anterior-temporal system, most prominently between left perirhinal/entorhinal cortices and medial prefrontal cortex. Furthermore, correlation analysis in this group revealed decreasing functional connectivity between bilateral perirhinal/entorhinal cortices, anterior hippocampus and posterior-medial regions with increasing levels of phosphorylated tau. The amyloid-b-positive individuals with mild cognitive impairment mostly exhibited reduced connectivity between the medial temporal lobe and posterior-medial regions, predominantly between the anterior hippocampus and posterior cingulate cortex. In addition, they showed hyperconnectivity within the medial temporal lobe and its immediate proximity. Lower medial temporal-cortical functional connectivity networks resulting from the group comparisons of cognitively unimpaired individuals were associated with reduced memory performance and more rapid longitudinal memory decline as shown by linear mixed-effects regression analysis. Finally, we found that reduced medial temporal-cortical connectivity in mildly cognitively impaired individuals was related to reduced entorhinal thickness and white matter integrity of the parahippocampal cingulum and the fornix. No such relationships were found in cognitively unimpaired individuals. In conclusion, our findings show that the earliest changes in preclinical Alzheimer's disease might involve decreased connectivity within the anterior-temporal system, and early changes in connectivity might be related to memory impairment, but not to structural changes. With disease progression and increased tau pathology, medial temporal functional connectivity with posterior-medial regions seems to be increasingly impaired. In individuals with mild cognitive impairment, reduced functional connectivity is associated with structural brain changes as well as the emergence of locally increased connectivity patterns. Thus, functional connectivity between the medial temporal lobe and the anterior-temporal and posterior-medial system could serve as stage-specific functional markers in early Alzheimer's disease.
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| 3. |
- Borland, Emma, et al.
(författare)
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The age-related effect on cognitive performance in cognitively healthy elderly is mainly caused by underlying AD pathology or cerebrovascular lesions : implications for cutoffs regarding cognitive impairment
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As research in treatments for neurocognitive diseases progresses, there is an increasing need to identify cognitive decline in the earliest stages of disease for initiation of treatment in addition to determining the efficacy of treatment. For early identification, accurate cognitive tests cutoff values for cognitive impairment are essential. METHODS: We conducted a study on 297 cognitively healthy elderly people from the BioFINDER study and created subgroups excluding people with signs of underlying neuropathology, i.e., abnormal cerebrospinal fluid [CSF] β-amyloid or phosphorylated tau, CSF neurofilament light (neurodegeneration), or cerebrovascular pathology. We compared cognitive test results between groups and examined the age effect on cognitive test results. RESULTS: In our subcohort without any measurable pathology (n = 120), participants achieved better test scores and significantly stricter cutoffs for cognitive impairment for almost all the examined tests. The age effect in this subcohort disappeared for all cognitive tests, apart from some attention/executive tests, predominantly explained by the exclusion of cerebrovascular pathology. CONCLUSION: Our study illustrates a new approach to establish normative data that could be useful to identify earlier cognitive changes in preclinical dementias. Future studies need to investigate if there is a genuine effect of healthy aging on cognitive tests or if this age effect is a proxy for higher prevalence of preclinical neurodegenerative diseases.
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| 4. |
- Fjalldal, Sigridur, et al.
(författare)
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Brain white matter lesions are associated with reduced hypothalamic volume and cranial radiotherapy in childhood-onset craniopharyngioma
- 2021
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 94:1, s. 48-57
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Tidskriftsartikel (refereegranskat)abstract
- Context: White matter lesions (WML) are caused by obstruction of small cerebral vessels associated with stroke risk. Craniopharyngioma (CP) patients suffer from increased cerebrovascular mortality. Objective: To investigate the effect of reduced HT volume and cranial radiotherapy (CRT) on WML in childhood-onset CP patients. Design: A cross-sectional study of 41 patients (24 women) surgically treated childhood-onset CP in comparison to controls. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Methods: With magnetic resonance imaging (MRI), we analysed qualitative measurement of WML based on the visual rating scale of Fazekas and quantitative automated segmentation of WML lesion. Also, measurement HT volume and of cardiovascular risk factors were analysed. Results: Patients had a significant increase in WML volume (mL) (P =.001) compared to controls. Treatment with cranial radiotherapy (CRT) vs no CRT was associated with increased WML volume (P =.02) as well as higher Fazekas score (P =.001). WML volume increased with years after CRT (r = 0.39; P =.02), even after adjustment for fat mass and age. A reduced HT volume was associated with increased WML volume (r = −0.61, P <.001) and explained 26% of the variation (r2 = 0.26). Altogether, 47% of the WML volume was explained by age at investigation, HT volume and CRT. Patients with more WML also had higher cardiovascular risk. Conclusions: CRT may be associated directly with increased WML volume or indirectly with reduced HT volume associated with higher cardiovascular risk. Risk factors should be carefully monitored in these patients.
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| 5. |
- Gertje, Eske Christiane, et al.
(författare)
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Association of Enlarged Perivascular Spaces and Measures of Small Vessel and Alzheimer Disease
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:2, s. 193-202
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relationship between enlarged perivascular spaces (EPVS) and measures of Alzheimer disease (AD), small vessel disease (SVD), cognition, vascular risk factors, and neuroinflammation, we tested associations between EPVS and different relevant neuroimaging, biochemical, and cognitive variables in 778 study participants. METHODS: Four hundred ninety-nine cognitively unimpaired (CU) individuals, 240 patients with mild cognitive impairment, and 39 patients with AD from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study were included. EPVS with diameter >1 mm in centrum semiovale (CSO), basal ganglia (BG), and hippocampus (HP); hippocampal volume; white matter lesions (WML); and other SVD markers were determined from MRI. CSF levels of β-amyloid42 (Aβ42), phosphorylated tau, total tau, and neuroinflammatory markers; amyloid accumulation determined with [18F]-flutemetamol PET; and vascular risk factors and results from cognitive tests were determined and collected. RESULTS: EPVS in CSO, BG, and HP were associated with WML volume and Fazekas score in individuals without dementia. No associations were found between EPVS and CSF Aβ42, total tau and phosphorylated tau, neuroinflammatory markers, vascular risk factors, and cognitive tests. EPVS in HP were associated with hippocampal atrophy. In a matched group of individuals with AD and CU, EPVS in HP were associated with AD diagnosis. CONCLUSIONS: EPVS are related to SVD, also in early disease stages, but the lack of correlation with cognition suggests that their importance is limited. Our data do not support a role for EPVS in early AD pathogenesis.
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| 6. |
- Gustavsson, Anna Märta, et al.
(författare)
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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
- 2020
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:1, s. 52-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.
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| 7. |
- Harper, Luke, et al.
(författare)
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Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:18, s. 3937-3944
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Tidskriftsartikel (refereegranskat)abstract
- The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD). This study aims to determine the prevalence and impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images of individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer's disease (n = 92, 73.3), and healthy controls (n = 110, 62.4) were evaluated using standard protocol for hemispheric paracingulate sulcal presence. No difference in left hemisphere paracingulate sulcal frequency was observed between groups; 0.72, 0.79, and 0.70, respectively, in the bvFTD, Alzheimer's disease, and healthy control groups, (P = 0.3). A significant impact of right (but not left) hemispheric paracingulate sulcation on age at disease onset was identified in bvFTD (mean 60.4 years where absent vs. 63.8 where present [P = 0.04, Cohen's d = 0.42]). This relationship was not observed in Alzheimer's disease. These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease providing a gross morphological example of brain reserve.
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| 8. |
- Håkansson, Claes, et al.
(författare)
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Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
- 2022
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32, s. 1127-1134
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's kappa (dichotomized data), Cohen's kappa(w), and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as kappa/kappa(w) >= 0.80 and ICC >= 0.80 (significance level at 95% CI >= 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's kappa. All raters achieved adequate agreement expressed as Cohen's kappa(w) and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.
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| 9. |
- Håkansson, Claes, et al.
(författare)
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Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment
- 2021
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:2, s. 666-673
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). Methods Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n= 111) and after (n= 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. Results We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p< 0.001), WMC from 69 to 86% (p< 0.01), and GCA from 54 to 82% (p< 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p< 0.001). There was a significant increase in TPR from 10 to 55% for MTA. Conclusion This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse.
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| 10. |
- Johansson Lindgren, Jessica, et al.
(författare)
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Anfall av gåshud visade sig vara anti-LGI-1-encefalit
- 2020
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Ingår i: Läkartidningen. - 0023-7205. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Anti-LGI-1 encephalitis is a type of autoimmune encephalopathy, where antibodies react against the cell surface protein leucine-rich glioma inactivated protein 1 (LGI-1). It presents with a subacute confusion, changes in behaviour, short-term memory deficits and seizures. A piloerectile semiology is common, which has been described as reflecting insular ictal activity. Patients may have temporal lobe abnormalities on brain MRI and EEG. More than half of the patients with limbic encephalitis associated with anti-LGI1 antibodies have hyponatremia. The diagnosis of anti-LGI-1 encephalitis can be made by the detection of antibodies against LGI-1 in serum and/or cerebrospinal fluid. Prompt diagnosis and treatment are important to avoid long-term disability. This case report describes a man with episodes of goose bumps and mild confusion caused by anti-LGI-1 encephalitis.
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