31 results on '"Verhey, Frans R."'
Search Results
2. An Exploratory Study of the Development and Pilot Testing of an Interactive Visual Tool of Neuropsychological Test Results in Memory Clinics.
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Gruters, Angélique A. A., Ramakers, Inez H. G. B., Stiekema, Annemarie P. M., Verhey, Frans R. J., Kessels, Roy P. C., and de Vugt, Marjolein E.
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NEUROPSYCHOLOGICAL tests ,MEMORY testing ,PSYCHOLOGISTS ,PILOT projects ,SYSTEM integration ,COGNITION disorders diagnosis ,FAMILIES & psychology ,ALZHEIMER'S disease diagnosis ,COGNITION disorders ,RESEARCH ,ALZHEIMER'S disease ,FOCUS groups ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,MEMORY disorders ,COMMUNICATION ,PATIENT-professional relations ,PSYCHOLOGICAL factors - Abstract
Background: Neuropsychological feedback is an important part of the neuropsychological assessment process. However, patients have difficulties remembering this information.Objective: The aim of this study was to develop a web-based visual tool to improve the understanding of neuropsychological results, information retention, and psychologist-patient communication.Methods: The visual tool was developed and optimized using an iterative three-phase stepwise approach to determine its usability, technology acceptance, and feasibility in a memory clinic population. Feedback from different user perspectives (patients, family members, and psychologists) was obtained in each phase using a multimethod approach (e.g. a multidisciplinary brainstorm session, think-aloud sessions, focus groups). The prototype was subsequently tested in a pilot study.Results: The first phases offered insights that led to optimization of the prototype. On a scale ranging from 0 to 100, psychologists evaluated the usability as high [88.1±7.6,70-87]. During the pilot study, both patients and significant others gave positive feedback, but information retention in patients remained low. All participants thought the benefits of the visual tool included seeing cognitive strengths and weaknesses with a translation to daily life all at one glance and receiving feedback on paper to take home. Important barriers were mentioned by psychologists, such as a limited set of tests included and no integration with hospital systems.Conclusion: Overall, patients, family members, and psychologists reported that a visual display of the cognitive profile with insights into daily life had added value to clinical practice. Feedback from the pilot study was adopted in the tool for future implementation purposes. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment.
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Pagen, Linda H G, van de Ven, Vincent G, Gronenschild, Ed H B M, Priovoulos, Nikos, Verhey, Frans R J, and Jacobs, Heidi I L
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Background: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients.Objective: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance.Methods: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN.Results: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients.Conclusion: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]- Published
- 2020
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4. Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease.
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Geijselaers, Stefan L. C., Aalten, Pauline, Ramakers, Inez H. G. B., De Deyn, Peter Paul, Heijboer, Annemieke C., Koek, Huiberdina L., OldeRikkert, Marcel G. M., Papma, Janne M., Reesink, Fransje E., Smits, Lieke L., Stehouwer, Coen D. A., Teunissen, Charlotte E., Verhey, Frans R. J., van der Flier, Wiesje M., Biessels, Geert Jan, and Parelsnoer Institute Neurodegenerative Diseases study group
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CEREBROSPINAL fluid ,ALZHEIMER'S disease ,MAGNETIC resonance imaging ,MILD cognitive impairment ,DEMENTIA ,COGNITION disorders diagnosis ,BRAIN metabolism ,APOLIPOPROTEINS ,BRAIN ,CELLULAR signal transduction ,COGNITION disorders ,INSULIN ,NEUROPSYCHOLOGICAL tests ,NERVE tissue proteins ,PEPTIDES ,PSYCHOLOGICAL tests ,DISEASE complications - Abstract
Background: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD).Objective: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype.Methods: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau.Results: CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029).Conclusion: Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin. [ABSTRACT FROM AUTHOR]- Published
- 2018
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5. Tolerability and Safety of Souvenaid in Patients with Mild Alzheimer's Disease: Results of Multi-Center, 24-Week, Open-Label Extension Study
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Olde Rikkert, Marcel G.M., primary, Verhey, Frans R., additional, Blesa, Rafael, additional, von Arnim, Christine A.F., additional, Bongers, Anke, additional, Harrison, John, additional, Sijben, John, additional, Scarpini, Elio, additional, Vandewoude, Maurits F.J., additional, Vellas, Bruno, additional, Witkamp, Renger, additional, Kamphuis, Patrick J.G.H., additional, and Scheltens, Philip, additional
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- 2015
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6. Cost-Utility of Using Alzheimer's Disease Biomarkers in Cerebrospinal Fluid to Predict Progression from Mild Cognitive Impairment to Dementia.
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Handels, Ron L H, Wimo, Anders, Dodel, Richard, Kramberger, Milica G, Visser, Pieter Jelle, Molinuevo, José Luis, Verhey, Frans R J, and Winblad, Bengt
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Background: Diagnostic research criteria for Alzheimer's disease support the use of biomarkers in the cerebrospinal fluid (CSF) to improve the accuracy of the prognosis regarding progression to dementia for people with mild cognitive impairment (MCI).Objective: The aim of this study was to estimate the potential incremental cost-effectiveness ratio of adding CSF biomarker testing to the standard diagnostic workup to determine the prognosis for patients with MCI.Methods: In an early technology assessment, a mathematical simulation model was built, using available evidence on added prognostic value as well as expert opinion to estimate the incremental costs and quality-adjusted life years (QALYs) of 20,000 virtual MCI patients with (intervention strategy) and without (control strategy) relying on CSF, from a health-care sector perspective and with a 5-year time horizon.Results: Adding the CSF test improved the accuracy of prognosis by 11%. This resulted in an average QALY gain of 0.046 and € 432 additional costs per patient, representing an incremental cost-effectiveness ratio of € 9,416.Conclusion: The results show the potential of CSF biomarkers in current practice from a health-economics perspective. This result was, however, marked by a high degree of uncertainty, and empirical research is required into the impact of a prognosis on worrying, false-positive/negative prognosis, and stigmatization. [ABSTRACT FROM AUTHOR]- Published
- 2017
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7. Modifiable Risk Factors for Prevention of Dementia in Midlife, Late Life and the Oldest-Old: Validation of the LIBRA Index.
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Vos, Stephanie J. B., Van Boxtel, Martin P. J., Schiepers, Olga J. G., Deckers, Kay, De Vugt, Marjolein, Carriére, Isabelle, Dartigues, Jean-François, Peres, Karine, Artero, Sylvaine, Ritchie, Karen, Galluzzo, Lucia, Scafato, Emanuele, Frisoni, Giovanni B., Huisman, Martijn, Comijs, Hannie C., Sacuiu, Simona F., Skoog, Ingmar, Irving, Kate, O'donnell, Catherine A., and Verhey, Frans R. J.
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DEMENTIA prevention ,AGING ,DEMENTIA risk factors ,MIDDLE age ,ALZHEIMER'S disease risk factors ,PHYSICAL activity measurement ,HYPERTENSION epidemiology ,AGE distribution ,COMPARATIVE studies ,DEMENTIA ,MENTAL depression ,DIABETES ,HEALTH planning ,RESEARCH methodology ,MEDICAL cooperation ,QUESTIONNAIRES ,RESEARCH ,SMOKING ,EVALUATION research - Abstract
Background: Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individual's prevention potential for dementia.Objective: We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old.Methods: 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individual's LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16).Results: In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia.Conclusion: LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-β.
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Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., and LeARN project
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LEUKOENCEPHALOPATHIES ,HIPPOCAMPUS (Brain) ,AMYLOIDOSIS diagnosis ,NEURODEGENERATION ,MAGNETIC resonance imaging ,ALZHEIMER'S disease ,ANTHROPOMETRY ,BRAIN ,CEREBRAL hemorrhage ,COGNITION ,NEUROPSYCHOLOGICAL tests ,PEPTIDES ,SENSORY perception ,REGRESSION analysis ,CROSS-sectional method ,CEREBRAL small vessel diseases - Abstract
Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Differences in Nutritional Status Between Very Mild Alzheimer's Disease Patients and Healthy Controls
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Olde Rikkert, Marcel G.M., primary, Verhey, Frans R., additional, Sijben, John W.C., additional, Bouwman, Femke H., additional, Dautzenberg, Paul L.J., additional, Lansink, Mirian, additional, Sipers, Walther M.W., additional, van Asselt, Dieneke Z.B., additional, van Hees, Anneke M.J., additional, Stevens, Martijn, additional, Vellas, Bruno, additional, and Scheltens, Philip, additional
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- 2014
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10. Amyloid-β Interacts with Blood-Brain Barrier Function in Dementia: A Systematic Review
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Burgmans, Saartje, primary, van de Haar, Harm J., additional, Verhey, Frans R. J., additional, and Backes, Walter H., additional
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- 2013
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11. Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory Clinic Patients in a Prospective Cohort.
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Handels, Ron L. H., Joore, Manuela A., Vos, Stephanie J. B., Aalten, Pauline, Ramakers, Inez H. G. B., Rikkert, Marcel Olde, Scheltens, Philip, Jansen, Willemijn J., Visser, Pieter-Jelle, van Berckel, Bart M. N., van Domburg, Peter, Smid, Machiel, Hoff, Erik, Hoogmoed, Jan, Bouwman, Femke, Claassen, Jurgen, Leentjens, Albert F. G., Wolfs, Claire A. G., Severens, Johan L., and Verhey, Frans R. J.
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ALZHEIMER'S disease research ,BRAIN disease research ,BIOMARKERS ,CEREBROSPINAL fluid ,LUMBAR puncture ,ALZHEIMER'S disease ,LONGITUDINAL method ,MEMORY disorders ,PROGNOSIS ,PSYCHOLOGICAL tests ,REFERENCE values ,DISEASE complications - Abstract
Background: Limited information is available on short-term prognosis of Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) in addition to routine diagnostic workup.Objective: This study aims to investigate the added prognostic value of AD CSF biomarkers.Methods: In a prospective cohort study, clinical experts predicted cognitive and functional symptoms in 114 memory clinic patients by assessing comprehensive routine diagnostic test information (patient history, and physical, neurological, psychiatric, neuropsychological, and MRI examinations), without and with CSF biomarkers. The reference standard was the 'observed clinically relevant decline' using baseline and 1- and 2-year follow-up information.Results: Decline over a 2-year period was observed in 51% of all participants (3% in SMC, 48% in MCI, 90% in mild dementia). In the total sample, the accuracy of predicted decline did not differ significantly between routine assessment without (79% correctly predicted) and with (74% correctly predicted) CSF biomarkers. Subgroup analyses revealed 25 (83%) correct predictions in SMC, 30 (68%) in MCI, and 35 (88%) in dementia without the use of CSF; and 21 (70%), 27 (61%), and 36 (90%), respectively, with the use of CSF in addition to the routine assessment.Conclusion: AD CSF biomarkers did not increase accuracy of 2-year prognosis of cognitive and functional decline when added to routine diagnostic workup. This suggests that the standard diagnostic workup without CSF biomarkers allows fairly accurate predictions for the short-term course of symptoms. Routine AD biomarkers in CSF have limited prognostic value over 2 years in persons with a suspected cognitive disorder. [ABSTRACT FROM AUTHOR]- Published
- 2016
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12. The Effect of Psychological Distress and Personality Traits on Cognitive Performances and the Risk of Dementia in Patients with Mild Cognitive Impairment.
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Ramakers, Inez H. G. B., Honings, Steven T. H., Ponds, Rudolf W., Aalten, Pauline, Köhler, Sebastian, Verhey, Frans R. J., Visser, Pieter Jelle, and Sebastian, Köhler
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MILD cognitive impairment ,PERSONALITY development ,INDIVIDUALITY ,NEURODEGENERATION ,EMOTIONS - Abstract
Background: The relation between psychological distress, personality traits, and cognitive decline in cognitively impaired patients remains unclear.Objective: To investigate the effect of psychological distress and personality traits on cognitive functioning in subjects with mild cognitive impairment (MCI); and to investigate the predictive accuracy of these factors for the development of dementia.Methods: MCI patients (n = 343, age: 60.9±9.9 years, 38% female, and MMSE score: 28.1±1.9) were included from the Maastricht memory clinic. All patients underwent a standardized neuropsychological assessment (including tests for measuring mental speed (Trail Making Test (TMT) part A and Stroop Color Word Test (SCWT) part I), executive functioning (TMT part B and SCWT part III), memory (15-Word Learning Tests), and verbal fluency (1-minute animals)), CT or MRI, and blood assessment. The Dutch Personality Questionnaire (DPQ) and the 90-items Symptom Check List (SCL-90) were used to measure personality traits and psychological distress. Conversion to dementia was assessed two, five, and ten years after baseline. The mean follow-up period was 6.7±3.4 years.Results: The Psychoneuroticism score of the SCL-90 was associated with slower performances on SCWT part I and TMT part A. The subdomain Neuroticism of the DPQ was also associated with slower scores on the TMT part A. At follow-up, 85 (25.9%) subjects had developed dementia. The SCL-90 total score, and the subscales, Anxiety, Somatization, Insufficiency in thought and action, and Sleeping problems were associated with a decreased risk for developing (AD-type) dementia.Conclusion: Psychological distress negatively affected information processing speed, but was not associated with an increased risk of developing dementia in patients with MCI. [ABSTRACT FROM AUTHOR]- Published
- 2015
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13. The influence of co-morbidity and frailty on the clinical manifestation of patients with Alzheimer's disease.
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Oosterveld, Saskia M, Kessels, Roy P C, Hamel, Renske, Ramakers, Inez H G B, Aalten, Pauline, Verhey, Frans R J, Sistermans, Nicole, Smits, Lieke L, Pijnenburg, Yolande A, van der Flier, Wiesje M, Olde Rikkert, Marcel G M, and Melis, René J F
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- 2014
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14. Amyloid-[beta] Interacts with Blood-Brain Barrier Function in Dementia: A Systematic Review.
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Burgmans, Saartje, van de Haar, Harm J, Verhey, Frans R J, and Backes, Walter H
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- 2013
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15. Natural progression model of cognition and physical functioning among people with mild cognitive impairment and alzheimer's disease.
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Handels, Ron L H, Xu, Weili, Rizzuto, Debora, Caracciolo, Barbara, Wang, Rui, Winblad, Bengt, Verhey, Frans R J, Severens, Johan L, Fratiglioni, Laura, Joore, Manuela A, and Wimo, Anders
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ALZHEIMER'S disease ,COGNITION disorders ,HEALTH planning ,LONGITUDINAL method ,NEUROPSYCHOLOGICAL tests ,MOTOR ability ,PSYCHOLOGICAL tests ,SURVIVAL analysis (Biometry) ,TIME ,DISEASE progression - Abstract
Background: Empirical models of the natural history of Alzheimer's disease (AD) may help to evaluate new interventions for AD.Objective: We aimed to estimate AD-free survival time in people with mild cognitive impairment (MCI) and decline of cognitive and physical function in AD cases.Methods: Within the Kungsholmen project, 153 incident MCI and 323 incident AD cases (international criteria) were identified during 9 years of follow-up in a cognitively healthy cohort of elderly people aged ≥75 at baseline (n = 1,082). Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and daily life function was evaluated with the Katz index of activities of daily living (ADL) at each follow-up examination. Data were analyzed using parametric survival analysis and mixed effect models.Results: Median AD-free survival time of 153 participants with incident MCI was 3.5 years. Among 323 incident AD cases, the cognitive decline was 1.84 MMSE points per year, which was significantly associated with age. Physical functioning declined by 0.38 ADL points per year and was significantly associated with age, education, and MMSE, but not with gender.Conclusion: Elderly people with MCI may develop AD in approximately 3.5 years. Both cognitive and physical function may decline gradually after AD onset. The empirical models can be used to evaluate long-term disease progression of new interventions for AD. [ABSTRACT FROM AUTHOR]- Published
- 2013
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16. Dynamic cerebral autoregulation in subjects with Alzheimer's disease, mild cognitive impairment, and controls: evidence for increased peripheral vascular resistance with possible predictive value.
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Gommer ED, Martens EG, Aalten P, Shijaku E, Verhey FR, Mess WH, Ramakers IH, Reulen JP, Gommer, Erik D, Martens, Esther G H J, Aalten, Pauline, Shijaku, Eri, Verhey, Frans R J, Mess, Werner H, Ramakers, Inez H G B, and Reulen, Jos P H
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Cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer's disease (AD). We hypothesized that cerebral autoregulation is impaired in patients with AD compared to subjects with mild cognitive impairment (MCI) and controls. Dynamic cerebral autoregulation (dCA) was investigated in 17 AD patients, 19 MCI subjects, and 20 controls (C). Groups were matched for age, gender, and level of education. Electrocardiogram and non-invasive finger arterial blood pressure were measured and transcranial doppler ultrasonography was used to measure cerebral blood flow velocity in right and left middle cerebral artery (MCA). Cerebrovascular resistance index (CVRi) was also computed. dCA in supine position was quantified based on spontaneous blood pressure variations by computation of the linear transfer function between arterial blood pressure and MCA cerebral blood flow velocity. dCA gain and phase were evaluated for different frequency bands. Results were also evaluated using a 3-parameter windkessel model (WKM). CVRi was significantly higher in AD (2.9 ± 0.2) compared to both MCI (2.3 ± 0.1, p = 0.02) and C (2.1 ± 0.1 mmHgs/cm, p = 0.002). Five MCI patients who converted to AD during the course of the study also had higher CVRi compared to non-converters (2.8 ± 0.6 versus 2.1 ± 0.5 mmHgs/cm, p < 0.05). No significant differences in dCA gain and phase were found. In terms of the WKM approach, in the order C→MCI→AD groups showed about equal arterial resistance and peripheral compliance, but increased peripheral vasculature resistance (26 ± 2 versus 36 ± 3 mmHgs/ml in C resp. AD, p = 0.004). In conclusion, AD patients compared to MCI patients and controls have increased CVRi, whereas dCA parameters do not seem to differentiate AD patients. For MCI patients, CVRi might have predictive value in developing AD. [ABSTRACT FROM AUTHOR]
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- 2012
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17. Distinct Patterns Link the BDNF Val66Met Polymorphism to Alzheimer's Disease Pathology.
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Riphagen JM, van Hooren RWE, Kenis G, Verhey FRJ, and Jacobs HIL
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- Amyloid beta-Peptides cerebrospinal fluid, Apolipoproteins E genetics, Biomarkers cerebrospinal fluid, Humans, Inflammation complications, Peptide Fragments cerebrospinal fluid, tau Proteins cerebrospinal fluid, tau Proteins genetics, Alzheimer Disease psychology, Brain-Derived Neurotrophic Factor genetics, Cognitive Dysfunction psychology
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The brain-derived neurotropic growth factor (BDNF) gene has been linked to dementia, inflammation, and Apolipoprotein E (APOE) ɛ4 status. We used cerebrospinal fluid (CSF) amyloid-β (Aβ)42 and phosphorylated tau (p-tau) to investigate associations with BDNF polymorphisms and modifications by APOE ɛ4 or inflammation in a memory clinic population (n = 114; subjective cognitive decline, mild cognitive impairment, Alzheimer's disease). We found distinct pathways to Alzheimer's disease pathology: Val-Met displayed lower CSF-Aβ42 in APOE ɛ4+ carriers, independent of p-tau, while Val-Val displayed greater p-tau at higher IL-6 and sub-threshold Aβ42. This may contribute to resolving some inconsistencies in the BDNF literature and provide possible inroads to specific Aβ and tau interventions depending on BDNF polymorphism.
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- 2022
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18. Association Between Cognition, Health Related Quality of Life, and Costs in a Population at Risk for Cognitive Decline.
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Janssen N, Handels RL, Wimo A, Antikainen R, Laatikainen T, Soininen H, Strandberg T, Tuomilehto J, Kivipelto M, Evers SMAA, Verhey FRJ, and Ngandu T
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- Activities of Daily Living psychology, Cognition, Humans, Risk Factors, Cognitive Dysfunction epidemiology, Cognitive Dysfunction psychology, Quality of Life psychology
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Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition., Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline., Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n = 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms., Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p < 0.001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p < 0.001) decrease in HRQoL utilities., Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.
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- 2022
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19. The Role of Vascular Risk Factors in Biomarker-Based AT(N) Groups: A German-Dutch Memory Clinic Study.
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Kučikienė D, Costa AS, Banning LCP, van Gils V, Schulz JB, Ramakers IHGB, Verhey FRJ, Vos SJB, and Reetz K
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- Amyloid beta-Peptides cerebrospinal fluid, Atrophy, Biomarkers cerebrospinal fluid, Female, Humans, Male, Peptide Fragments cerebrospinal fluid, Risk Factors, tau Proteins cerebrospinal fluid, Alcoholism, Alzheimer Disease diagnostic imaging, Alzheimer Disease epidemiology, Alzheimer Disease pathology, Carotid Stenosis, Cognitive Dysfunction cerebrospinal fluid
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Background: The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association., Objective: To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context., Methods: We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands). Subjects were older than 45 years and had available data on demographics, VRFs, CSF AD biomarkers, and MRI. We categorized individuals in normal AD biomarkers, non-AD change, and AD-continuum groups based on amyloid (A), tau (T), and neurodegeneration (N) status in CSF and MRI. Regression models were corrected for age, sex, and site., Results: We included 838 participants (mean age 68.7, 53.2% male, mean MMSE 24.9). The most common VRFs were smoking (60.9%), hypertension (54.6%), and dyslipidemia (37.8%). Alcohol abuse and smoking were most frequent in the non-AD-change group, and coronary heart disease and carotid artery stenosis in the AD continuum group. Higher rates of depression were found in the normal AD biomarkers group. Parietal atrophy and cortical microbleeds were specific for the AD continuum group. Carotid artery stenosis was associated with pathological Aβ42 and T-tau values, and diabetes and alcohol abuse were associated with worse medial temporal atrophy and atrial fibrillation, with worse cognition., Conclusion: VRFs are common in memory clinic patients, showing differences across the AT(N) biomarker groups. This is important for prevention and individualized treatment of dementia.
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- 2022
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20. Elevated Activity of the Sympathetic Nervous System Is Related to Diminished Practice Effects in Memory: A Pilot Study.
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Pagen LHG, Smeets T, Schmiedek L, Yassa MA, Verhey FRJ, and Jacobs HIL
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- Adult, Aged, Female, Healthy Volunteers, Humans, Linear Models, Male, Middle Aged, Pilot Projects, Saliva chemistry, Saliva metabolism, Salivary alpha-Amylases metabolism, Stress, Psychological metabolism, Stress, Psychological physiopathology, Sympathetic Nervous System physiology
- Abstract
Background: Reductions in memory practice effects have gained interest as risk factor for future cognitive decline. Practice effects vary with age and can be moderated by factors such as individual variability in arousal or stress experience acting as an additional cognitive load., Objective: In the current pilot study, we examined whether sympathetic nervous system activation moderates the relationship between age and practice effects., Methods: Thirty cognitively healthy individuals aged 40-70 years performed a mnemonic discrimination task twice. Salivary alpha amylase (sAA) samples were obtained at different time points as a proxy of sympathetic activity. Spearman correlations examined the relation between practice effects and sAA. Subsequently, age by sAA interactions on practice scores were explored with bootstrapped linear regression models. Additionally, participants were divided in learners (exhibiting practice effects) and non-learners based on the difference in mnemonic discrimination performance., Results: Higher age and baseline SNS activity were independently related to lower practice effects. The non-learners showed significantly higher sAA scores at all time points compared to learners. Among the learners, baseline-adjusted lower levels of sAA after encoding were associated with greater practice effects, particularly in middle-aged individuals. No such interaction was observed for non-learners., Conclusion: These results show that higher baseline sympathetic activation is associated with worse practice effects independently of age. Additionally, in a subgroup of middle-aged learners practice effects were observed when sympathetic activity remained low during learning. These findings suggest that elevated sympathetic nervous system activation may be a promising indicator of imminent cognitive decline.
- Published
- 2021
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21. Depressive Symptoms in Mild Cognitive Impairment and the Risk of Dementia: A Systematic Review and Comparative Meta-Analysis of Clinical and Community-Based Studies.
- Author
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Tan EYL, Köhler S, Hamel REG, Muñoz-Sánchez JL, Verhey FRJ, and Ramakers IHGB
- Subjects
- Disease Progression, Humans, Prodromal Symptoms, Risk Factors, Cognitive Dysfunction epidemiology, Cognitive Dysfunction psychology, Dementia epidemiology, Depression diagnosis
- Abstract
Background: Affective symptoms are considered a risk factor or prodromal symptom for dementia. Recent reviews indicate that depressive symptoms predict progression from mild cognitive impairment (MCI) to dementia, but results need to be further explored., Objective: To investigate the effect of depressive symptoms on the development of dementia in people with MCI, and explore potential sources of between-study variability, including study setting by a systematic review and meta-analysis., Methods: Databases were searched for prospective studies defining people with MCI at baseline, investigating dementia at follow-up and giving information about depressive symptoms. Two authors independently extracted data from the studies and rated the methodological quality. Meta-analyses were conducted using random-effect models to yield pooled risk ratios (RR). Meta-regression analyses tested differences between clinical and community-based studies and other sources of heterogeneity., Results: Thirty-five studies, representing 14,158 individuals with MCI, were included in the meta-analysis. Depressive symptoms in MCI predicted dementia in 15 community-based studies (RR = 1.69, 95% CI 1.49-1.93, I2 = 0.0%), but not in 20 clinical studies (RR = 1.02, 95% CI 0.92-1.14, I2 = 73.0%). Further investigation of this effect showed that the mean age of community-based studies was significantly higher than of clinical studies but neither this nor other study characteristics explained variability in study outcomes., Conclusions: Depressive symptoms are associated with an increased risk of conversion from MCI to dementia in community-based studies. In contrast, evidence in clinical populations was insufficient with high heterogeneity.
- Published
- 2019
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22. Modifiable Risk Factors Explain Socioeconomic Inequalities in Dementia Risk: Evidence from a Population-Based Prospective Cohort Study.
- Author
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Deckers K, Cadar D, van Boxtel MPJ, Verhey FRJ, Steptoe A, and Köhler S
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Dementia therapy, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk Factors, Risk Reduction Behavior, Dementia economics, Dementia epidemiology, Healthcare Disparities economics, Healthcare Disparities trends, Population Surveillance, Social Class
- Abstract
Background: Differences in dementia risk across the gradient of socioeconomic status (SES) exist, but their determinants are not well understood., Objective: This study investigates whether health conditions and lifestyle-related risk factors explain the SES inequalities in dementia risk., Methods: 6,346 participants from the English Longitudinal Study of Ageing were followed up from 2008/2009 until 2014/2015. We used Cox regression adjusted for age, gender, wealth/education, and clustering at the household level to examine the association between SES markers (wealth, education) and time to dementia in a structural equation model including potential mediation or effect modification by a weighted compound score of twelve modifiable risk and protective factors for dementia ('LIfestyle for BRAin health' (LIBRA) score)., Results: During a median follow-up of 6 years, 192 individuals (3.0%) developed dementia. LIBRA scores decreased with increasing wealth and higher educational level. A one-point increase in the LIBRA score was associated with a 13% increase in dementia risk (hazard ratio (HR) = 1.13, 95% confidence interval 1.07-1.19). Higher wealth was associated with a decreased dementia risk (HR = 0.58, 0.39-0.85). Mediation analysis showed that 52% of the risk difference between the highest and lowest wealth tertile was mediated by differences in LIBRA (indirect effect: HR = 0.75, 0.66-0.85). Education was not directly associated with dementia (HR = 1.05, 0.69-1.59), but was a distal risk factor for dementia by explaining differences in wealth and LIBRA scores (indirect effect high education: HR = 0.92, 0.88-0.95)., Conclusion: Socioeconomic differences in dementia risk can be partly explained by differences in modifiable health conditions and lifestyle factors.
- Published
- 2019
- Full Text
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23. Association Between Proxy- or Self-Reported Cognitive Decline and Cognitive Performance in Memory Clinic Visitors.
- Author
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Gruters AAA, Ramakers IHGB, Verhey FRJ, Köhler S, Kessels RPC, and de Vugt ME
- Subjects
- Aged, Aged, 80 and over, Cognitive Dysfunction diagnosis, Cognitive Dysfunction epidemiology, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Netherlands epidemiology, Prospective Studies, Ambulatory Care Facilities, Cognitive Dysfunction psychology, Memory physiology, Proxy psychology, Psychomotor Performance physiology, Self Report
- Abstract
Background: It is uncertain whether self- and proxy-reported cognitive decline in older adults reflect an actual objective cognitive dysfunction in the clinical sense, and if these are predictive for developing dementia., Objective: The aim of the present study is to investigate the cross-sectional and longitudinal relation between subjective cognitive decline and objective cognitive performance, depressive symptoms, and to determine the predictive value for development of dementia., Methods: We included 405 patients without dementia at first visit from the Maastricht memory clinic participating in a longitudinal cohort study. Subjective cognitive decline was measured using a self- and proxy-report questionnaire. All patients underwent a standardized neuropsychological assessment. Follow-up assessments were performed yearly for three consecutive years, and once after five years., Results: Subjective cognitive decline was associated with lower cognitive performance and more depressive symptoms. When comparing self- (n = 342, 84%) and proxy-reported decline (n = 110, 27%), it was shown that proxy reports were associated with a more widespread pattern of lower cognitive performance. In participants without cognitive impairment proxy-reported decline was not associated with depressive symptoms. In contrast, self-reported decline was associated with a stable course of depressive symptoms at follow-up. Proxy-reported cognitive decline (HR = 1.76, 95% CI = 1.12- 2.78), and mutual complaints (HR = 1.73, CI:1.09- 2.76) predicted incident dementia while self-reported decline did not reach statistical significance (HR = 1.26, 95% CI = 0.65- 2.43)., Conclusion: Proxy-reported cognitive decline was consistently associated with lower cognitive performance and conversion to dementia over 5 years. Self-reported cognitive decline in patients without cognitive impairment might indicate underlying depressive symptoms and thus deserve clinical attention as well.
- Published
- 2019
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24. Impact of Untimely Access to Formal Care on Costs and Quality of Life in Community Dwelling People with Dementia.
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Janssen N, Handels RL, Sköldunger A, Woods B, Jelley H, Edwards RT, Orrell M, Selbæk G, Røsvik J, Gonçalves-Pereira M, Marques MJ, Zanetti O, Portolani E, Irving K, Hopper L, Meyer G, Bieber A, Stephan A, Kerpershoek L, Wolfs CAG, de Vugt ME, Verhey FRJ, and Wimo A
- Subjects
- Aged, Aged, 80 and over, Cost of Illness, Dementia economics, Female, Geriatric Assessment, Health Services Needs and Demand, Humans, Independent Living, Male, Middle Aged, Needs Assessment, Time-to-Treatment, Dementia therapy, Health Care Costs, Health Services Accessibility, Quality of Life
- Abstract
Background: Access to formal care is not always timely and a better understanding on the impact of untimely access is needed., Objective: To examine, from a societal perspective, the impact of untimely access to formal care in terms of total costs and quality of life over one year in community dwelling people with dementia., Methods: Within the Actifcare study, needs, resource use, and quality of life were observed for one year in a cohort of 451 community dwelling people with dementia in 8 European countries. Untimely access to care was operationalized as having at least one unmet need for care identified by the Camberwell Assessment of Need for the Elderly (CANE) instrument. Two regression models were built for both total costs and quality of life measured by the EQ-5D-5L, one using sum of unmet needs and one using a predefined selection of need items., Results: Unmet needs were not associated with higher total costs but they were associated with a lower quality of life of people with dementia. Of all CANE items, only an unmet need for "company" was significantly related to lower total costs., Conclusion: Total costs did not seem to differ between participants with unmet and met needs. Only few associations between specific unmet needs and costs and quality of life were found. Furthermore, quality of life of people with dementia decreases when multiple unmet needs are experienced, indicating that assessing and meeting needs is important to improve quality of life.
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- 2018
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25. The Progression of Dementia and Cognitive Decline in a Dutch 2-Year Cohort Study of People with Young-Onset Dementia.
- Author
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Gerritsen AAJ, Bakker C, Verhey FRJ, Bor H, Pijnenburg YAL, de Vugt ME, and Koopmans RTCM
- Subjects
- Adult, Age of Onset, Aged, Cohort Studies, Disease Progression, Female, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Netherlands epidemiology, Cognition Disorders epidemiology, Dementia epidemiology
- Abstract
Background: The progression of dementia in people with young-onset dementia (YOD) is relatively unknown., Objective: To investigate the progression of dementia and cognitive decline in the three most common subtypes in YOD and to explore which factors are associated with this course., Methods: The course of dementia was examined in 198 people with YOD. The primary outcomes were cognitive function, as assessed by the Mini-Mental State Examination (MMSE) and dementia severity, as assessed by the Global Deterioration Scale (GDS). Mixed-model analyses were used to explore factors associated with the course of dementia of the diagnostic sub-types., Results: The mean overall two-year progression of dementia severity was 0.9 GDS points, this was a statistically significant change (p = 0.012) and was not significant different for the three dementia subtypes. The mean overall two-year decline in cognitive function was 1.6 points on the MMSE. The differences in cognitive decline were statistically significant (p = 0.046) among the three diagnosis groups, AD participants showed the greatest decline, of 2.3 points. In addition to lower education (p = 0.010), higher scores on the Neuropsychiatric Inventory (NPI) sub-syndromes psychosis (p < 0.001) and hyperactivity (p = 0.002) were associated with higher rates of cognitive decline. In contrast, higher scores on the NPI affect cluster were associated with lower levels of cognitive decline (p < 0.001)., Conclusion: Different YOD subtypes show different rates of decline in cognitive functioning, and this decline seems less progressive compared to those observed in studies in late-onset AD. Further research is needed to evaluate whether managing neuropsychiatric symptoms can positively influence the decline of cognitive function.
- Published
- 2018
- Full Text
- View/download PDF
26. Alzheimer's Disease Biomarkers Have Distinct Associations with Specific Hippocampal Subfield Volumes.
- Author
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Müller-Ehrenberg L, Riphagen JM, Verhey FRJ, Sack AT, and Jacobs HIL
- Subjects
- Aged, Aged, 80 and over, Amyloid beta-Peptides cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction pathology, Female, Hippocampus diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments cerebrospinal fluid, tau Proteins cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease pathology, Biomarkers cerebrospinal fluid, Hippocampus metabolism, Hippocampus pathology
- Abstract
Measures of amyloid-β (Aβ) and phosphorylated tau (p-tau) concentrations in cerebrospinal fluid are extensively used for diagnostic and research purposes in Alzheimer's disease (AD) as correlates of cortical thinning and cognitive outcomes. The present study investigated the relationship of Aβ and p-tau with hippocampal subfield volumes Cornu Ammonis (CA) 1-4, dentate gyrus (DG), and subiculum. Subfields were segmented from T1-weighted images from the ADNI-population using FreeSurfer v6. Linear and polynomial regression models revealed distinct associations of Aβ and p-tau with subfield volumes. Aβ had a quadratic relationship with all hippocampal subfield volumes and the inflection point was higher than the validated cut-off for Aβ. For p-tau the relationships were linear, except for CA3, in which it was quadratic. For the CA1 and CA3, these quadratic relationships with Aβ were only observed when p-tau was low. Amyloid and p-tau contributed equally to the explained variance in CA4 and DG volume. Subicular volume was best explained by Aβ alone. These biomarker relationships with hippocampal subfield volumes seem to mirror the hippocampal-specific topography of Aβ and tau reported in neuropathological staging models. In addition, using continuous values of Aβ reveals positive patterns with imaging markers for individuals around the positivity threshold that would be masked when using dichotomized biomarker groups, which can be important for early detection and accurate inclusion of potential participants at risk for AD in clinical trials.
- Published
- 2018
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27. White matter hyperintensities are positively associated with cortical thickness in Alzheimer's disease.
- Author
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Jacobs HI, Clerx L, Gronenschild EH, Aalten P, and Verhey FR
- Subjects
- Aged, Frontal Lobe pathology, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Parietal Lobe pathology, Temporal Lobe pathology, Alzheimer Disease pathology, Brain pathology, Cognitive Dysfunction pathology, Nerve Fibers, Myelinated pathology
- Abstract
White matter hyperintensities are associated with an increased risk of Alzheimer's disease (AD). White matter hyperintensities are believed to disconnect brain areas. We examined the topographical association between white matter hyperintensities and cortical thickness in controls, mild cognitive impairment (MCI), and AD patients. We examined associations between white matter hyperintensities and cortical thickness among 18 older cognitively healthy participants, 18 amnestic MCI, and 17 mild AD patients. These associations were cluster-size corrected for multiple comparisons. In controls, a positive association between white matter hyperintensities and cortical thickness was found in lateral temporal gyri. In MCI patients, white matter hyperintensities were positively related to cortical thickness in frontal, temporal, and parietal areas. Positive associations between white matter hyperintensities and cortical thickness in AD patients were confined to parietal areas. The results of the interaction group by white matter hyperintensities on cortical thickness were consistent with the findings of positive associations in the parietal lobe for MCI and AD patients separately. In the frontal areas, controls and AD patients showed inverse associations between white matter hyperintensities and cortical thickness, while MCI patients still showed a positive association. These results suggest that a paradoxical relationship between white matter hyperintensities and cortical thickness could be a consequence of neuroinflammatory processes induced by AD-pathology and white matter hyperintensities. Alternatively, it might reflect a region-specific and disease-stage dependent compensatory hypertrophy in response to a compromised network.
- Published
- 2014
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28. The association between APOE ε4 and Alzheimer-type dementia among memory clinic patients is confined to those with a higher education. The DESCRIPA Study.
- Author
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Vermeiren AP, Bosma H, Visser PJ, Zeegers MP, Graff C, Ewers M, Frisoni GB, Frölich L, Hampel H, Jones RW, Kehoe PG, Lenoir H, Minthon L, Nobili FM, Olde Rikkert M, Rigaud AS, Scheltens P, Soininen H, Spiru L, Tsolaki M, Wahlund LO, Vellas B, Wilcock G, Elias-Sonnenschein LS, and Verhey FR
- Subjects
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease epidemiology, Alzheimer Disease psychology, Cohort Studies, DNA genetics, Female, Genotype, Humans, Longitudinal Studies, Male, Memory Disorders epidemiology, Memory Disorders psychology, Middle Aged, Proportional Hazards Models, Prospective Studies, Sex Factors, Survival Analysis, Alzheimer Disease genetics, Apolipoprotein E4 genetics, Educational Status, Gene-Environment Interaction, Memory Disorders genetics
- Abstract
We assessed the interaction between the APOE ε4 allele and education level in the etiology of Alzheimer's disease (AD) among memory clinic patients from the multicenter DESCRIPA study. Subjects (n = 544) were followed for 1 to 5 years. We used Cox's stratified survival modeling, adjusted for age, gender, and center. APOE ε4 predicted the onset of AD-type dementia in middle (HR 3.45 95% CI 1.79-6.65, n = 222) and high (HR 3.67 95% CI 1.36-9.89, n = 139) but not in low educated subjects (HR 0.81, 95% CI 0.38-1.72, n = 183). This suggests that mechanisms in developing Alzheimer-type dementia may differ between educational groups that raises questions related to Alzheimer-type dementia prevention.
- Published
- 2013
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29. Neuropsychiatric symptoms in Alzheimer's disease and vascular dementia.
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Echávarri C, Burgmans S, Uylings H, Cuesta MJ, Peralta V, Kamphorst W, Rozemuller AJ, and Verhey FR
- Subjects
- Aged, Aged, 80 and over, Behavioral Symptoms diagnosis, Female, Humans, Logistic Models, Male, Mental Disorders diagnosis, Neuropsychological Tests, Psychiatric Status Rating Scales, Retrospective Studies, Severity of Illness Index, Alzheimer Disease complications, Behavioral Symptoms etiology, Dementia, Vascular complications, Mental Disorders etiology
- Abstract
Neuropsychiatric symptoms (NPSs) have a large impact on the quality of life of patients with dementia. A few studies have compared neuropsychiatric disturbances between dementia subtypes, but the results were conflicting. In the present study, we investigated whether the prevalence of NPSs differs between Alzheimer's disease (AD) and vascular dementia (VaD). The merit of our study is that we used clinical as well as histopathological information to differentiate between dementia subtypes. This retrospective descriptive study comprised 80 brains obtained from donors to the Netherlands Brain Bank between 1984 and 2010. These donors were diagnosed postmortem with AD (n = 40) or VaD (n = 40). We assessed the presence of NPSs by reviewing the information found in the patients' medical files. The most prevalent symptom in the sample as a whole was agitation (45 cases, 57.0%), followed by depression (33, 41.2%) and anxiety (28, 35.4%). Our study tried to contribute to the discussion by including, for the first time in the literature, a sample of AD and VaD patients with neuropathologically confirmed diagnoses. Since no significant differences were found between AD and VaD patients, we suggest that the prevalence of NPSs cannot be predicted from the diagnosis of AD or VaD.
- Published
- 2013
- Full Text
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30. Co-occurrence of different pathologies in dementia: implications for dementia diagnosis.
- Author
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Echávarri C, Burgmans S, Caballero MC, García-Bragado F, Verhey FR, and Uylings HB
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease complications, Alzheimer Disease diagnosis, Alzheimer Disease epidemiology, Comorbidity, Dementia complications, Diagnosis, Differential, Female, Frontotemporal Dementia complications, Frontotemporal Dementia diagnosis, Frontotemporal Dementia epidemiology, Humans, Lewy Body Disease complications, Lewy Body Disease diagnosis, Lewy Body Disease epidemiology, Male, Middle Aged, Neurodegenerative Diseases complications, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases epidemiology, Prion Diseases complications, Prion Diseases diagnosis, Prion Diseases epidemiology, Young Adult, Dementia diagnosis, Dementia epidemiology
- Abstract
The standard for differentiating between dementia subtypes is currently based on neuropathological changes and follows traditional nosological classifications. However, the high incidence of comorbid neuropathologies complicates the differentiation between dementia diagnoses in the clinic. The aim of this study was to investigate the grades of agreement between clinical and neuropathological diagnoses in neurodegenerative disorders, to compare them with rates found in previous studies, and to propose implications for dementia diagnostics. Patients, who donated their brains to the Brain Bank of Navarre (Pamplona, Spain), had been diagnosed with a neurodegenerative disorder during life (clinical diagnosis) and postmortem (neuropathological diagnosis). We studied a sample of patients with a short average time interval between the last clinical assessment and death (4.6 months). Overall, there was a mean grade of agreement of 44.0% between the clinical diagnosis and the pure neuropathological diagnosis (i.e., without co-morbid neuropathological disorders). This grade of agreement differed between dementia subtypes: e.g., 85% for prion disease, 49% for Alzheimer's disease, and 0% for Lewy body dementia. Our data confirm that co-occurrence of multiple neuropathological disorders is very common in individuals with dementia, and that the underlying neuropathology often differs from the neuropathology implied by the clinical diagnosis. These findings support a multidimensional approach to diagnosing dementia, in which dementia syndromes are not categorized into diagnostic subtypes, but are seen as syndromes characterized by a combination of various neuropathological dimensions.
- Published
- 2012
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31. Increasing the diagnostic accuracy of medial temporal lobe atrophy in Alzheimer's disease.
- Author
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Jacobs HI, Van Boxtel MP, van der Elst W, Burgmans S, Smeets F, Gronenschild EH, Verhey FR, Uylings HB, and Jolles J
- Subjects
- Aged, Atrophy diagnosis, Atrophy etiology, Brain Mapping, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging methods, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, ROC Curve, Alzheimer Disease complications, Alzheimer Disease diagnosis, Cognition Disorders diagnosis, Cognition Disorders etiology, Temporal Lobe pathology
- Abstract
Medial temporal lobe (MTL) atrophy is considered to be one of the most important predictors of Alzheimer's disease (AD). This study investigates whether atrophy in parietal and prefrontal areas increases the predictive value of MTL atrophy in three groups of different cognitive status. Seventy-five older adults were classified as cognitively stable (n = 38) or cognitively declining (n = 37) after three years follow-up. At follow-up, the grey matter of the MTL, inferior prefrontal cortex (IPC), and inferior parietal lobule (IPL) was delineated on MRI scans. Six years later, a dementia assessment resulted in distinguishing and separating a third group (n = 9) who can be considered as preclinical AD cases at scan time. Ordinal logistic regressions analysis showed that the left and right MTL, as well as the right IPC and IPL accurately predicted group membership. Receiver Operating Curves showed that the MTL was best in distinguishing cognitively stable from cognitively declining individuals. The accuracy of the differentiation between preclinical AD and cognitively stable participants improved when MTL and IPL volumes were combined, while differentiating preclinical AD and cognitively declined participants was accomplished most accurately by the combined volume of all three areas. We conclude that depending on the current cognitive status of an individual, adding IPL or IPC atrophy improved the accuracy of predicting conversion to AD by up to 22%. Diagnosis of preclinical AD may lead to more false positive outcomes if only the MTL atrophy is considered.
- Published
- 2011
- Full Text
- View/download PDF
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