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01 januari 2023, Item does not contain fulltext, Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.

Item does not contain fulltext, PURPOSE: Cognitive diagnostic work-up in primary care is not always physically feasible, owing to chronic disabilities and/or travel restrictions. The identification of dementia might be facilitated with diagnostic instruments that are time efficient and easy to perform, as well as useful in the remote setting. We assessed whether the Telephone Interview for Cognitive Status (TICS) might be a simple and accurate alternative for remote diagnostic cognitive screening in primary care. METHODS: We administered the TICS (range, 0-41) for 810 of 1,473 older people aged 84.5 (SD, 2.4) years. We scrutinized electronic health records for participants with TICS scores ≤30 and for a random sample of participants with TICS scores >30 for a dementia diagnosis using all data from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial for 8-12 years of follow-up. We used multiple imputation to correct for verification bias. RESULTS: Of the 810 participants, 155 (19.1%) had a TICS score ≤30, and 655 (80.9%) had a TICS score >30. Electronic health records yielded 8.4% (13/154) dementia diagnoses for participants with TICS ≤30 vs none with TICS >30. Multiple imputation for TICS >30 yielded a median of 7/655 (1.1%; interquartile range, 5-8) estimated dementia cases. After multiple imputation, the optimal cutoff score was ≤29, with mean sensitivity 65.4%, specificity 87.8%, positive predictive value 11.9%, negative predictive value 99.0%, and area under the curve 77.4% (95% CI, 56.3%-90.0%). CONCLUSIONS: In the present older population, the TICS performed well as a diagnostic screening instrument for excluding dementia and might be particularly useful when face-to-face diagnostic screening is not feasible in family practice or research settings. The potential reach to large numbers of people at low cost could contribute to more efficient medical management in primary care.

Item does not contain fulltext, Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development.

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Contains fulltext : 191110.pdf (Publisher’s version ) (Open Access), OBJECTIVE: To assess whether apathy and depressive symptoms are independently associated with incident dementia during 6-year follow-up in a prospective observational population-based cohort study. METHODS: Participants were community-dwelling older people in the Prevention of Dementia by Intensive Vascular Care trial, aged 70-78 years, without dementia at baseline. Apathy and depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Dementia during follow-up was established by clinical diagnosis confirmed by an independent outcome adjudication committee. Hazard ratios (HRs) were calculated using Cox regression analyses. Given its potentially strong relation with incipient dementia, the GDS item referring to memory complaints was assessed separately. RESULTS: Dementia occurred in 232/3,427 (6.8%) participants. Apathy symptoms were associated with dementia (HR 1.28, 95% confidence interval [CI] 1.12-1.45; p < 0.001), also after adjustment for age, sex, Mini-Mental State Examination score, disability, and history of stroke or cardiovascular disease (HR 1.21, 95% CI 1.06-1.40; p = 0.007), and in participants without depressive symptoms (HR 1.26, 95% CI 1.06-1.49; p = 0.01). Depressive symptoms were associated with dementia (HR 1.12, 95% CI 1.05-1.19), also without apathy symptoms (HR 1.16, 95% CI 1.03-1.31; p = 0.015), but not after full adjustment or after removing the GDS item on memory complaints. CONCLUSIONS: Apathy and depressive symptoms are independently associated with incident dementia in community-dwelling older people. Subjective memory complaints may play an important role in the association between depressive symptoms and dementia. Our findings suggest apathy symptoms may be prodromal to dementia and might be used in general practice to identify individuals without cognitive impairment at increased risk of dementia.

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Contains fulltext : 193392.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, Importance: Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies. Objective: To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia. Data Sources: Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases. Study Selection: Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia. Data Extraction and Synthesis: PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second. Main Outcomes and Measures: Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models. Results: The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1

Contains fulltext : 193563.pdf (publisher's version ) (Open Access), Background: Previous findings suggest that apathy symptoms independently of depressive symptoms measured using the Geriatric Depression Scale (GDS) are associated with cardiovascular disease (CVD) in older individuals. Aims: To study whether apathy and depressive symptoms in older people are associated with future CVD, stroke, and mortality using individual patient-data meta-analysis. Methods: Medline, Embase, and PsycInfo databases up to September 3, 2013, were systematically searched without language restrictions. We sought prospective studies with older (mean age >/=65 years) community-dwelling populations in which the GDS was employed and subsequent stroke and/or CVD were recorded to provide individual participant data. Apathy symptoms were defined as the three apathy-related subitems of the GDS, with depressive symptoms the remaining items. We used myocardial infarction (MI), stroke, and all-cause mortality as main outcomes. Analyses were adjusted for age, sex, and MI/stroke history. An adaptation of the Newcastle-Ottawa scale was used to evaluate bias. Hazard ratios were calculated using one-stage random-effect Cox regression models. Results: Of the 52 eligible studies, 21 (40.4%) were included, comprising 47,625 older people (mean age [standard deviation] 74 [7.4] years), over a median follow-up of 8.8 years. Participants with apathy symptoms had a 21% higher risk of MI (95% confidence interval [CI] 1.08-1.36), a 37% higher risk of stroke (95% CI 1.18-1.59), and a 47% higher risk of all-cause mortality (95% CI 1.38-1.56). Participants with depressive symptoms had a comparably higher risk of stroke (HR 1.36, 95% CI 1.18-1.56) and all-cause mortality (HR 1.44, 95% CI 1.35-1.53), but not of MI (HR 1.08, 95% CI 0.91-1.29). Associations for isolated apathy and isolated depressive symptoms were comparable. Sensitivity analyses according to risk of bias yielded similar results. Conclusion: Our findings stress the clinical importance of recognizing apathy independent

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Item does not contain fulltext, Macro-vascular artifacts are a common arterial spin labeling (ASL) finding in populations with prolonged arterial transit time (ATT) and result in vascular regions with spuriously increased cerebral blood flow (CBF) and tissue regions with spuriously decreased CBF. This study investigates whether there is an association between the spatial signal distribution of a single post-label delay ASL CBF image and ATT. In 186 elderly with hypertension (46% male, 77.4 +/- 2.5 years), we evaluated associations between the spatial coefficient of variation (CoV) of a CBF image and ATT. The spatial CoV and ATT metrics were subsequently evaluated with respect to their associations with age and sex - two demographics known to influence perfusion. Bland-Altman plots showed that spatial CoV predicted ATT with a maximum relative error of 7.6%. Spatial CoV was associated with age (beta = 0.163, p = 0.028) and sex (beta = -0.204, p = 0.004). The spatial distribution of the ASL signal on a standard CBF image can be used to infer between-participant ATT differences. In the absence of ATT mapping, the spatial CoV may be useful for the clinical interpretation of ASL in patients with cerebrovascular pathology that leads to prolonged transit of the ASL signal to tissue.

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Item does not contain fulltext, OBJECTIVE: Use of antihypertensive medication (AHM) is potentially associated with a reduced risk of dementia. Both calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs) are suggested to have a more pronounced protective effect. We aimed to study the association between different classes of AHM and dementia in older people. METHODS: A subgroup of community-dwelling older people using AHM included in the 'Prevention of Dementia by Intensive Vascular Care' randomized controlled trial was studied. Incident dementia rates in participants with different AHM classes (mono and combination therapy) were compared with dementia rates in participants with any other AHM. RESULTS: At baseline, 1951 participants (55.3%) used AHM [mean age, 74.4 year (SD 2.5); mean SBP, 156.4 mmHg (SD 21.5)]. In total, 986 participants (50.5%) used beta-blockers, 798 diuretics (40.9%), 623 angiotensin- converting enzyme inhibitors (31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile range 6.0-7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use of CCBs [hazard ratio 0.56, 95% confidence interval (95% CI) 0.36-0.87] and ARBs (hazard ratio 0.60, 95% CI 0.37-0.98) were independently associated with a decreased risk of dementia. The association of CCBs with dementia was most apparent in participants without a history of cardiovascular disease (hazard ratio 0.38, 95% CI 0.18-0.81) and with uncontrolled hypertension (hazard ratio 0.26, 95% CI 0.11-0.61). SBP was not significantly lower in participants using CCBs or ARBs. CONCLUSION: Both use of CCBs and ARBs are independently associated with a decreased risk of dementia in older people.

Item does not contain fulltext, OBJECTIVE: To assess whether intensive vascular care in GP practices can prevent dementia in a population of community-dwelling older people. METHOD: This pragmatic cluster-randomised open-label study (ISRCTN29711771) was conducted in persons aged 70-78 years who were registered with Dutch GP practices. The only exclusion criteria were a diagnosis of dementia and limited life expectancy. Practices were randomly assigned to an intervention arm or a control arm. Participants in the interventional arm underwent a cardiovascular check-up every 4 months for six years by a practice nurse. Primary outcomes were cumulative incidence of dementia and functional limitations. Main secondary outcomes were the incidence of cardiovascular disease and mortality. RESULTS: Between June 2006 and March 2009, 116 GP practices (3526 participants) were recruited and randomly assigned: 63 (1890 participants) to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6.7 years. In this period, dementia was diagnosed in 121/1853 (6.5%) participants in the intervention group and in 112/1601 (7.0%) participants in the control group. This difference was not significant (hazard ratio 0.92, 95% CI 0.71-1.19). No differences were found with regard to functional decline, incident cardiovascular disease and mortality. CONCLUSION: Long-term intensive vascular care for community-dwelling elderly patients, provided in a primary care setting, does not result in a reduced incidence of dementia, functional limitations or mortality. There is, however, possibly an effect in elderly patients with untreated or sub-optimally treated hypertension; this warrants further research.

Contains fulltext : 180451.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND AND PURPOSE: This study aimed to evaluate the effect of a nurse-led multidomain cardiovascular intervention on white matter hyperintensity (WMH) progression and incident lacunar infarcts in community-dwelling elderly with hypertension. METHODS: The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. General practices were assigned by computer-generated randomization to 6-year nurse-led, multidomain intensive vascular care or standard care. Of 3526 preDIVA participants, 195 nondemented participants with a systolic blood pressure >/=140 mm Hg were consecutively recruited to undergo magnetic resonance imaging at 2 to 3 and 5 to 6 years after baseline. WMH volumes were measured automatically, lacunar infarcts assessed visually, blinded to treatment allocation. RESULTS: One hundred and twenty-six participants were available for longitudinal analysis (64 intervention and 62 control). Annual WMH volume increase in milliliter was similar for intervention (mean=0.73, SD=0.84) and control (mean=0.70, SD=0.59) participants (adjusted mean difference, -0.08 mL; 95% confidence interval, -0.30 to 0.15; P=0.50). Analyses suggested greater intervention effects with increasing baseline WMH volumes (P for interaction=0.03). New lacunar infarcts developed in 6 (9%) intervention and 2 (3%) control participants (odds ratio, 2.2; 95% confidence interval, 0.4-12.1; P=0.36). CONCLUSIONS: Nurse-led vascular care in hypertensive community-dwelling older persons did not diminish WMH accumulation over 3 years. However, our results do suggest this type of intervention could be effective in persons with high WMH volumes. There was no effect on lacunar infarcts incidence but numbers were low. CLINICAL TRIAL INFORMATION: URL: http://www.isrctn.com/ISRCTN29711771. Unique identifier: ISRCTN29711771.

Item does not contain fulltext, BACKGROUND: Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a population of community-dwelling older people. METHODS: In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70-78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score [ALDS]) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. FINDINGS: Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6.7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio [HR] 0.92, 95% CI 0.71-1.19; p=0.54). Mean ALDS scores measured during follow-up did not differ between groups (85.7 [SD 6.8] in the intervention group and 85.7 [7.1] in the control group; adjusted mean difference -0.02, 95% CI -0.38 to 0.42; p=0.93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0.98, 95% CI 0.80-1.18; p=0.8

Contains fulltext : 154731.PDF (publisher's version ) (Open Access), PURPOSE: The current study assesses the feasibility and value of crushed cerebral blood flow (CBFcrushed) and arterial transit time (ATT) estimations for large clinical imaging studies in elderly with hypertension. MATERIAL AND METHODS: Two pseudo-continuous arterial spin labeling (ASL) scans with (CBFcrushed) and without flow crushers (CBFnon-crushed) were performed in 186 elderly with hypertension, from which CBF and ATT maps were calculated. Standard flow territory maps were subdivided into proximal, intermediate and distal flow territories, based on the measured ATT. The coefficient of variation (CV) and physiological correlations with age and gender were compared between the three perfusion parameters. RESULTS: There was no difference in CV between CBFcrushed and CBFnon-crushed (15-24%, p>0.4) but the CV of ATT (4-9%) was much smaller. The total gray matter correlations with age and gender were most significant with ATT (p = .016 and p<.001 respectively), in between for CBFcrushed (p = .206 and p = .019) and least significant for CBFnon-crushed (p = .236 and p = .100). CONCLUSION: These data show the feasibility and added value of combined measurements of both crushed CBF and ATT for group analyses in elderly with hypertension. The obtained flow territories provide knowledge on vascular anatomy of elderly with hypertension and can be used in future studies to investigate regional vascular effects.

Item does not contain fulltext, BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. METHODS: We evaluated CMIs on 3 Tesla MRI in a population-based cohort of 194 nondemented older people (72-80 years) with systolic hypertension. Using a case-control design, participants with and without CMIs were compared on age, sex, cardiovascular risk factors, and white matter hyperintensity volume. RESULTS: We identified 23 CMIs in 12 participants (6%). CMIs were associated with older age, higher diastolic blood pressure, and a history of recent stroke. There was a trend for a higher white matter hyperintensity volume in participants with CMIs. CONCLUSIONS: We found an association of CMIs with clinical parameters, including age and cardiovascular risk factors. Although the prevalence of CMIs is relatively low, our results suggest that the study of CMIs in larger clinical studies is possible using 3 Tesla MRI. This opens the possibility of large-scale prospective investigation of the clinical relevance of CMIs in older people.