[How often do medical guidelines refer to articles written in Dutch?] / Hoe vaak verwijzen richtlijnen naar artikelen in hetNTvG?

OBJECTIVE: For Dutch medical guidelines, Dutch research articles published in the NTvG (NederlandsTijdschriftvoorGeneeskunde) and other medical journals are not searched systematically and are only used sporadically. Using these publications in the process of guideline development can be useful for recommendations regarding the Dutch context of care. In this research, we have investigated how often and in which parts of Dutch guidelines articles published in NTvG are used. DESIGN: We specifically investigated how often articles published in NTvG are mentioned in Dutch medical guidelines published on www.richtlijnendatabase.nl, that were developed in 2019, 2020 and 2021. METHOD: In all parts of new or revised Dutch medical guidelines published in these years on www.richtlijnendatabase.nl, we searched for references of articles published in NTvG. RESULTS: The results show that in 3% of all Dutch medical guidelines a reference to an article published in NTvG is made. These references were made in the literature summaries (21% of the references), the reflections on the literature for the Dutch context of care (48% of the references), or in other areas such as the introduction (10% of the references) or appendices (21% of the references). CONCLUSION: Articles published in NTvG may be relevant for making recommendations in Dutch medical guidelines, as these publications usually reflect the Dutch care context, and may do more so than research published in international journals. The results of this research show that the number of Dutch guidelines where these articles are used is limited. Dutch research articles may be a source of information that is yet to be tapped into.

Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia.

BACKGROUND: Research has shown that mixed dementia is more common than previously believed but little is known of its early stages. OBJECTIVE: To examine if incipient mixed dementia can be differentiated from incipient Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SVD) using neuropsychological tests, cerebrospinal fluid (CSF) markers, and magnetic resonance imaging markers. METHODS: We included 493 patients and controls from the Gothenburg MCI study and used the dementia groups for marker selection (CSF total-tau (T-tau), phospho-tau (P-tau), and amyloid-ß42 (Aß42), 11 neuropsychological tests, and 92 regional brain volumes) and to obtain cut-off values which were then applied to the MCI groups. RESULTS: Incipient mixed dementia was best differentiated from incipient AD by the Word fluency F-A-S test and the Trail making test A. CSF T-tau, P-tau, and Aß42 differentiated incipient mixed dementia from incipient SVD. CONCLUSION: Incipient mixed dementia is characterized by an AD-like biomarker profile and an SVD-like cognitive profile. Incipient mixed dementia can be separated from incipient AD and incipient SVD using CSF markers and cognitive testing.

Latent Cognitive Profiles Differ Between Incipient Alzheimer's Disease and Dementia with Subcortical Vascular Lesions in a Memory Clinic Population.

BACKGROUND: It is unclear if latent cognitive profiles can distinguish between dementia with subcortical vascular lesions and Alzheimer's disease (AD) at the incipient stage, and if they differ in performance from the Petersen subtypes. OBJECTIVE: To identify latent cognitive profiles in a naturalistic population of patients from a memory clinic sample, and investigate the derived classes not only in terms of conversion to AD, but also in terms of conversion to dementia with subcortical vascular lesions. Another objective was to compare the derived classes to the Petersen subtypes. METHODS: We performed a latent profile analysis (LPA) on standardized neuropsychological test scores from 476 memory clinic patients (age 64±8) without dementia, and analyzed progression to dementia after 2 years. RESULTS: The LPA resulted in two classes with impaired cognition (Amnestic and Slow/Dysexecutive) and two classes with normal cognition (Normal-Low and Normal-High cognition). Belonging to the Amnestic class predicted progression to all-cause dementia and to AD; belonging to the Slow/Dysexecutive class predicted progression to all-cause dementia, AD, and dementia with subcortical vascular lesions. Of the Petersen MCI subtypes, only amnestic multi-domain MCI predicted progression to all-cause dementia, AD, and dementia with subcortical vascular lesions. CONCLUSION: Latent cognitive profiles separated between AD and dementia with subcortical vascular lesions, while the Petersen subtypes did not. However, similar to the Petersen subtypes, LPA classes work better for ruling out progression to dementia than for case finding.

Better prognostic accuracy in younger mild cognitive impairment patients with more years of education.

INTRODUCTION: Age and years of education influence the risk of dementia and may impact the prognostic accuracy of mild cognitive impairment subtypes. METHODS: Memory clinic patients without dementia (N = 358, age 64.0 ± 7.9) were stratified into four groups based on years of age (≤64 and ≥65) and education (≤12 and ≥13), examined with a neuropsychological test battery at baseline and followed up after 2 years. RESULTS: The prognostic accuracy of amnestic multi-domain mild cognitive impairment for dementia was highest in younger patients with more years of education and lowest in older patients with fewer years of education. Conversely, conversion rates to dementia were lowest in younger patients with more years of education and highest in older patients with fewer years of education. DISCUSSION: Mild cognitive impairment subtypes and demographic information should be combined to increase the accuracy of prognoses for dementia.

Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels.

BACKGROUND/AIMS: The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels. METHODS: Memory clinic patients were followed for 2 (n = 317, age 63.7 ± 7.8) and 4-6 (n = 168, age 62.6 ± 7.4) years. We used 2.0, 1.5, and 1.0 standard deviations (SD) below the mean of normal controls (n = 120, age 64.1 ± 6.6) to categorize MCI and the MCI subtypes. Prognostic accuracy for dementia syndrome at follow-up was estimated. RESULTS: Amnestic multi-domain MCI (aMCI-md) significantly predicted dementia under all conditions, most markedly when speed/attention, language, or executive function was impaired alongside memory. For aMCI-md, sensitivity increased and specificity decreased when the cut-off was lowered from 2.0 to 1.5 and 1.0 SD. Non-subtyped MCI had a high sensitivity and a low specificity. CONCLUSION: Our results suggest that aMCI-md is the only viable subtype for predicting dementia for both follow-up times. Lowering the cut-off decreases the positive predictive value and increases the negative predictive value of aMCI-md. The results are important for understanding the clinical prognostic utility of MCI, and MCI as a non-progressive disorder.

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.

INTRODUCTION: Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications. METHODS: Memory clinic patients (n = 235) were classified as SCD (n = 122): subtle cognitive decline (n = 36) and mild cognitive impairment (n = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications. RESULTS: Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2. DISCUSSION: In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.

Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.

BACKGROUND/AIMS: In the quest for prevention or treatment, there is a need to find early markers for preclinical dementia. This study observed memory clinic patients with subjective cognitive impairment (SCI) and normal cognitive function at baseline. The primary aim was to address SCI as a potential risk factor for cognitive decline. The secondary aim was to address a potential relation between (1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory performance over the first 2 years of follow-up, with a possible cognitive decline after 6 years. METHODS: Eighty-one patients (mean age 61 years) were recruited from university memory clinics and followed up for 6 years. RESULTS: Eighty-six percent of the cohort remained cognitively stable or improved, 9% developed mild cognitive impairment, and only 5% (n = 4) developed dementia. Regression analysis revealed that low levels of Aß42 at baseline and memory decline during the first 2 years predicted dementia. When combined, these variables were associated with a 50% risk of developing dementia. CONCLUSIONS: Cognitive stability for 86% of the cohort suggests that SCI is predominantly a benign condition with regard to neuropathology. The low number of individuals who developed dementia limits the generalizability of the results and discussion of progression factors.

The Gothenburg MCI study: Design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.

There is a need for increased nosological knowledge to enable rational trials in Alzheimer's disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD + SVD = MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials.

Alzheimer's disease--subcortical vascular disease spectrum in a hospital-based setting: Overview of results from the Gothenburg MCI and dementia studies.

The ability to discriminate between Alzheimer's disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders. The studies, the first of which started in 1987, comprise inpatients with manifest dementia and patients seeking care for cognitive disorders at an outpatient memory clinic. This article gives an overview of the major published papers (neuropsychological, imaging/physiology, and neurochemical) of the studies including the ongoing Gothenburg MCI study. The main findings suggest that subcortical vascular disease with or without dementia exhibit a characteristic neuropsychological pattern of mental slowness and executive dysfunction and neurochemical deviations typical of white matter changes and disturbed blood-brain barrier function. Our findings may contribute to better healthcare for this underrecognized group of patients. The Gothenburg MCI study has also published papers on multimodal prediction of dementia, and cognitive reserve.

T-Tau is Associated with Objective Memory Decline Over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study.

BACKGROUND: There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. OBJECTIVE: The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. METHODS: 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. RESULTS: The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. CONCLUSIONS: The main finding that T-tau rather than amyloid-ß was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q)--a research tool discriminating between subjectively cognitively impaired patients and healthy controls.

BACKGROUND: Subjective cognitive impairment (SCI) is a potential early marker for actual cognitive decline. The cognitive manifestation of the SCI stage is, however, largely unknown. Self-report instruments developed especially for use in the SCI population are lacking, and many SCI studies have not excluded mild cognitive impairment and dementia. We developed and tested a patient-based questionnaire on everyday cognitive function aiming to discriminate between patients with subjective, but not objective, cognitive impairment and healthy controls. METHODS: Individuals experiencing cognitive impairment were interviewed to generate a pool of items. After condensing to 97 items, we tested the questionnaire in 93 SCI patients seeking care at a memory clinic (age M = 64.5 years, Mini-Mental State Examination (MMSE) M = 29.0) and 50 healthy controls (age M = 69.6 years, MMSE M = 29.3). Further item reduction was conducted to maximize that remaining items would discriminate between SCI patients and controls, using a conservative α level and requiring medium to high effect sizes. Internal consistency reliability and convergent validity was subsequently examined. RESULTS: Forty-five items discriminated between the groups, resulting in the Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q). Internal consistency was high and correlations to a single question on memory functioning were of medium to large sizes. Most remaining items were related to the memory domain. CONCLUSION: The SASCI-Q discriminates between SCI patients and healthy controls and demonstrates satisfying psychometric properties. The instrument provides a research method for examining SCI and forms a foundation for future examining which SCI symptoms predict objective cognitive decline. The cognitive manifestation of the SCI stage is mostly related to experiences of memory deficits.

Vascular disease, Alzheimer's disease biomarkers and cognition in mild cognitive impairment: additive or synergetic effects?

BACKGROUND/AIMS: To study how vascular disease and Alzheimer-typical biomarkers relate to cognitive performance in mild cognitive impairment (MCI). METHODS: Three groups diagnosed with MCI, one with vascular disease (MCI-vas, n = 61), one with Alzheimer-typical biomarkers (MCI-bio, n = 99) and one with both vascular disease and Alzheimer-typical biomarkers (MCI-vasbio, n = 56), were examined with a comprehensive neuropsychological test battery. RESULTS: The MCI-vas and MCI-bio groups performed quite similarly on the test battery, whereas the MCI-vasbio group tended to perform worse than the other groups. MCI-vasbio patients performed significantly worse on tests within all cognitive domains, with the most clear-cut differences on an executive test. CONCLUSIONS: Considering the small differences between MCI-vas and MCI-bio, vascular disease or biomarkers alone do not seem to be associated with a specific cognitive profile. The combination of vascular disease and Alzheimer-typical biomarkers, on the other hand, seems to be associated with more severe cognitive deficits. The difference in an aspect of executive functioning is interpreted as a synergetic effect.

Cognitive profiles of incipient dementia in the Goteborg MCI study.

OBJECTIVE: To study which cognitive profiles of incipient dementia strongest predict the conversion to Alzheimer's disease (AD) and mixed dementia (MD)/vascular dementia (VaD). METHODS: 260 subjects with mild cognitive impairment (MCI) were included in the study and 209 (79%) were followed up after 2 years. At baseline, the subjects were assessed with a neuropsychological battery covering the cognitive domains speed/attention, memory, visuospatial, language and executive functions. RESULTS: After 2 years, 9 subjects were considered normal, 148 had stationary MCI and 47 (23%) had converted to dementia. Twenty subjects were diagnosed with AD, 15 with MD and 9 with VaD. The others were 2 with unspecified dementias and 1 with primary progressive aphasia. Dementia converters had a high proportion of impairment in all cognitive domains. The profiles of incipient AD and MD/VaD differed, with memory, visuospatial and language symptoms preceding AD, and executive and speed/attention symptoms preceding MD/VaD. CONCLUSIONS: The risk of converting to dementia is increased when domains in addition to memory are impaired. The incipient AD and MD/VaD profiles differed quite clearly. Considering that the vascular group consisted of a majority of patients with MD, the differences are convincing - vascular disease seems to have an essential impact on cognition.

B-type natriuretic peptide plasma levels are elevated in subcortical vascular dementia.

High levels of B-type natriuretic peptide (BNP), a serum marker of congestive heart failure, are associated with an increased risk for cognitive decline. However, no study has yet assessed this marker in different subtypes of dementia. We tested the hypothesis that BNP has a more significant association with vascular dementia than Alzheimer disease. Plasma BNP was measured in 15 patients with subcortical vascular dementia, in 19 Alzheimer patients without evidence of vascular comorbidity, and in age-matched controls. Compared with controls (28+/-7 ng/l), BNP was elevated in subcortical vascular dementia (63+/-17 ng/l; P=0.03), but not in Alzheimer disease (36+/-5 ng/l). In conclusion, subcortical vascular dementia is indeed associated with moderately elevated BNP levels, whereas this could not be shown for Alzheimer disease. This probably reflects the larger cardiovascular burden in patients with subcortical vascular dementia.