Much is known about palliative care needs of persons with dementia and their family. Less is known about how to successfully implement models that address those needs. We present specialist models... Show moreMuch is known about palliative care needs of persons with dementia and their family. Less is known about how to successfully implement models that address those needs. We present specialist models in the Netherlands (2017-2018) and Northern Ireland (2016-2017) contrasting its evaluations. From implementation failure in the Netherlands compared with successful implementation in Northern Ireland, we learn that recognizing roles and competencies among all involved is essential in developing effective partnership relationships. All of this is facilitated by referral before the end of life and offering various training programs and in-patient and out-patient services and therapies to show benefits early. Show less
Buuren, C.P. van; Steen, J.T. van der; Olthof-Nefkens, M.; Bakker, C.; Koopmans, R.T.C.M.; Perry, M.; Kalf, J.G. 2023
Background:Persons with dementia are at risk of developing nutritional problems. Theoretical models on nutritional problems have been developed, but have not been evaluated with healthcare... Show moreBackground:Persons with dementia are at risk of developing nutritional problems. Theoretical models on nutritional problems have been developed, but have not been evaluated with healthcare professionals.Objective:This study aimed to explore the comprehensiveness and applicability of a theoretical model of nutritional problems in persons with dementia for daily nursing home practice.Methods:A qualitative design employing a combined deductive and inductive approach was used. Healthcare professionals were eligible to participate if they 1) had expert knowledge of and experience with nutritional problems related to dementia, and 2) worked in a nursing home affiliated with an academic network covering the east and south of the Netherlands. Three focus group interviews with 20 healthcare professionals from seven professions were held. We conducted thematic analysis and we compared themes with existing theoretical models from the literature.Results:We identified six themes, four of which corresponded with the existing models (observing and analysing nutritional problems; consequences of nutritional problems; functioning of the person with dementia; environmental factors). Interprofessional collaboration and ethical factors were identified as new themes. The analyses indicated interactions within each theme, between themes, and a bidirectional connection between themes.Conclusions:This study demonstrated the relevance of interprofessional collaboration and ethical considerations in nutritional problems related to dementia. It uncovered complex bidirectional relations within and between factors regarding nutritional problems. All aspects should be taken into account to minimize the consequences of nutritional problems for persons with dementia. Show less
Kok, F.K.; Leerdam, S.L. van; Lange, E.C.M. de 2022
Background: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co... Show moreBackground: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co-morbidity with Alzheimer's disease. So far, DMVs have not been evaluated in CAA. Objective: To evaluate DMVs in Dutch-type hereditary CAA (D-CAA) mutation carriers and controls, in relation to MRI markers associated with D-CAA. Methods: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density were quantified on 7 Tesla 3D susceptibility weighted MRI in pre-symptomatic D-CAA mutation carriers (n = 8), symptomatic D-CAA mutation carriers (n = 8), and controls (n = 25). HemorrhagicMRImarkers (cerebral microbleeds, intracerebral hemorrhages, cortical superficial siderosis, convexity subarachnoid hemorrhage), non-hemorrhagic MRI markers (white matter hyperintensities, enlarged perivascular spaces, lacunar infarcts, cortical microinfarcts), cortical grey matter perfusion, and diffusion tensor imaging parameters were assessed in D-CAA mutation carriers. Univariate general linear analysis was used to determine associations between DMV parameters and MRI markers. Results: QuantitativeDMVparameters length, tortuosity, inhomogeneity, and density did not differ between pre-symptomatic D-CAA mutation carriers, symptomatic D-CAA mutation carriers, and controls. No associations were found between DMV parameters and MRI markers associated with D-CAA.Conclusion: This study indicates that vascular amyloid-beta deposition does not affectDMVparameters. In patients with CAA, DMVs do not seem to play a role in the pathogenesis of MRI markers associated with CAA. Show less
Background: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed... Show moreBackground: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).Objective: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.Methods: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.Results: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.Conclusion: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy. Show less
Background: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular... Show moreBackground: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function.Objective: To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function.Methods: 160 outpatient clinic patients (68.8 +/- 8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker).Results: Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05).Conclusion: Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns. Show less
Jung, Y.J.; Viviano, R.P.; Rooden, S. van; Grond, J. van der; Rombouts, S.A.R.B.; Damoiseaux, J.S. 2021
Background: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership... Show moreBackground: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership may influence how arterial pressure affects cognitive functioning.Objective: To determine the role of region-specific WMH burden and APOE epsilon 4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD).Methods: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE epsilon 4 carriership moderated that mediation.Results: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLFWMH and the effect of MAP on SLF WMH were significant only in APOE epsilon 4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in epsilon 4 carriers.Conclusion: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia. Show less
Chatterjee, P.; Fagan, A.M.; Xiong, C.J.; McKay, M.; Bhatnagar, A.; Wu, Y.Q.; ... ; Dominantly Inherited Alzheimer Net 2021
Objective: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs).Methods: Plasma metabolites were measured using mass... Show moreObjective: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs).Methods: Plasma metabolites were measured using mass-spectrometry (AbsoluteIDQ (R) p400 HR kit) and were compared between pre-symptomatic D-CAA MCs (n= 9) and non-carriers (D-CAA NCs, n= 8) from the same pedigree. Metabolites that survived correction for multiple comparisons were further compared between D-CAA MCs and additional control groups (cognitively unimpaired adults).Results: 275 metabolites were measured in the plasma, 22 of which were observed to be significantly lower in the D-CAA MCs compared to D-CAA NCs, following adjustment for potential confounding factors age, sex, and APOE epsilon 4 (p < 00.05). After adjusting for multiple comparisons, only spermidine remained significantly lower in the D-CAA MCs compared to the D-CAA NCs (p < 0.00018). Plasma spermidine was also significantly lower in D-CAA MCs compared to the cognitively unimpaired young adult and older adult groups (p < 0.01). Spermidine was also observed to correlate with CSF A beta(40) (r(s) = 0.621, p = 0.024), CSF A beta(42) (r(s) = 0.714, p = 0.006), and brain A beta load (r(s) = -0.527, p = 0.030).Conclusion: The current study provides pilot data on D-CAA linked metabolite signals, that also associated with A beta neuropathology and are involved in several biological pathways that have previously been linked to neurodegeneration and dementia. Show less
Background: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies ... Show moreBackground: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking.Objective: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer's disease (AD) and controls.Methods: QoL was assessed annually in 138 individuals, using the EQ5D-utility-score (0-100) and the health-related Visual Analogue Scale (VAS, 0-100). Twenty-nine DLB patients (age 69 +/- 6), 68 AD patients (age 70 +/- 6), and 41 controls (age 70 +/- 5) were selected from the Dutch Parelsnoer Institute-Neurodegenerative diseases and Amsterdam Dementia Cohort. We examined clinical work-up over time as determinants of QoL, including cognitive tests, neuropsychiatric inventory, Geriatric Depression Scale (GDS), and disability assessment of dementia (DAD).Results: Mixed models showed lower baseline VAS-scores in DLB compared to AD and controls (AD: beta +/- SE = - 7.6 +/- 2.8, controls: beta +/- SE = -7.9 +/- 3.0, p < 0.05). An interaction between diagnosis and time since diagnosis indicated steeper decline on VAS-scores for AD patients compared to DLB patients (beta +/- SE = 2.9 +/- 1.5, p < 0.1). EQ5D-utility-scores over time did not differ between groups. Higher GDS and lower DAD-scores were independently associated with lower QoL in dementia patients (GDS: VAS beta +/- SE = -1.8 +/- 0.3, EQ5D-utility beta +/- SE = -3.7 +/- 0.4; DAD: VAS = 0.1 +/- 0.0, EQ5D-utility beta +/- SE = 0.1 +/- 0.1, p < 0.05). No associations between cognitive tests and QoL remained in the multivariate model.Conclusion: QoL is lower in DLB, while in AD QoL shows steeper decline as the disease advances. Our results indicate that non-cognitive symptoms, more than cognitive symptoms, are highly relevant as they impact QoL. Show less
Bulk, M.; Kenkhuis, B.; Graaf, L.M. van der; Goeman, J.J.; Natte, R.; Weerd, L. van der 2018
Anatomical, diffusion tensor (DTI), and resting-state functional MRI (rs-fMRI) of 30 patients with early stage AD, 23 with bvFTD, and 35 control subjects were collected and used to calculate... Show moreAnatomical, diffusion tensor (DTI), and resting-state functional MRI (rs-fMRI) of 30 patients with early stage AD, 23 with bvFTD, and 35 control subjects were collected and used to calculate measures of structural and functional tissue status. All measures were used separately or selectively combined as predictors for training an elastic net regression classifier. Each classifier's ability to accurately distinguish dementia-types was quantified by calculating the area under the receiver operating characteristic curves (AUC). Overlapping clinical symptoms often complicate differential diagnosis between patients with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Magnetic resonance imaging (MRI) reveals disease specific structural and functional differences that aid in differentiating AD from bvFTD patients. However, the benefit of combining structural and functional connectivity measures to-on a subject-basis-differentiate these dementia-types is not yet known. Combining functional and structural connectivity measures improve dementia-type differentiations and may contribute to more accurate and substantiated differential diagnosis of AD and bvFTD patients. Imaging protocols for differential diagnosis may benefit from also including DTI and rs-fMRI. Highest AUC values for AD and bvFTD discrimination were obtained when mean diffusivity, full correlations between rs-fMRI-derived independent components, and fractional anisotropy (FA) were combined (0.811). Similarly, combining gray matter density (GMD), FA, and rs-fMRI correlations resulted in highest AUC of 0.922 for control and bvFTD classifications. This, however, was not observed for control and AD differentiations. Classifications with GMD (0.940) and a GMD and DTI combination (0.941) resulted in similar AUC values (p = 0.41). METHODS BACKGROUND/OBJECTIVE CONCLUSION RESULTS Show less
Bulk, M.; Kenkhuis, B.; Graaf, L.M. van der; Goeman, J.J.; Natte, R.; Weerd, L. van der 2018
The value of iron-based MRI changes for the diagnosis and staging of Alzheimer's disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study... Show moreThe value of iron-based MRI changes for the diagnosis and staging of Alzheimer's disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study determined the cortical distribution pattern of MRI contrast changes in cortical regions selected based on the known distribution pattern of tau pathology and investigated whether MRI contrast changes reflect the underlying AD pathology in the different lobes. T-2*-weighted MRI was performed on postmortem cortical tissue of controls, late-onset AD (LOAD), and early-onset AD (EOAD) followed by histology and correlation analyses. Combining ex vivo high-resolution MRI and histopathology revealed that: 1) LOAD and EOAD have a different distribution pattern of AD pathological hallmarks and MRI contrast changes over the cortex, with EOAD showing more severe MRI changes; 2) per lobe, severity of AD pathological hallmarks correlates with iron accumulation, and hence with MRI. Therefore, iron-sensitive MRI sequences allow detection of the cortical distribution pattern of AD pathology ex vivo. Show less
Mahinrad, S.; Vriend, A.E.; Jukema, J.W.; Heemst, D. van; Sattar, N.; Blauw, G.J.; ... ; Sabayan, B. 2017
