From Normal Cognition to Cognitive Impairment and Dementia: Impact of Orthostatic Hypotension.
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ABSTRACT:
SUBMITTER: Xia X
PROVIDER: S-EPMC8357050 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
From Normal Cognition to Cognitive Impairment and Dementia: Impact of Orthostatic Hypotension.
Xia Xin X Wang Rui R Vetrano Davide L DL Grande Giulia G Laukka Erika J EJ Ding Mozhu M Fratiglioni Laura L Qiu Chengxuan C
Hypertension (Dallas, Tex. : 1979) 20210706 3
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Project description:BackgroundOrthostatic hypotension (OH) has been cross-sectionally and longitudinally related to dementia in the general population. Whether OH contributes to clinical progression to mild cognitive impairment (MCI) or dementia is less certain. Also, differences in risk of progression between patients with early OH (EOH) versus delayed and/or prolonged OH (DPOH) are unclear.ObjectiveAssess the prevalence of EOH and DPOH, investigate the longitudinal association between EOH and DPOH and either incident MCI or dementia.Methods1,882 patients from the Amsterdam Dementia Cohort [64±8 years; 43% female; n = 500 with subjective cognitive decline (SCD), n = 341 MCI, n = 758 Alzheimer's disease (AD), n = 49 vascular dementia (VaD), n = 146 frontotemporal dementia (FTD), n = 88 Lewy body dementia (DLB)]. Definition OH: systolic blood pressure (BP) drop≥20 mmHg and/or a diastolic BP drop≥10 mmHg at 1 and/or 3 minutes after standing. EOH: OH only at 1 minute, DPOH: OH at (1 and) 3 minutes.ResultsPrevalence OH: 19% SCD, 28% MCI, 41% dementia. Compared to SCD, odds of having OH were highest in patients with VaD and DLB; ORs (95% CI) were 2.6 (1.4-4.7) and 5.1 (3.1-8.4), respectively. After a mean (SD) follow-up of 2.2 (1.4) years, 105 (22%) of SCD or MCI patients showed clinical progression. Compared to patients without OH, those with DPOH had an increased risk of progression; hazard ratio (95% CI) was 1.7 (1.1-2.7), and those with EOH did not; 0.8 (0.3-1.9).ConclusionCompared to SCD, prevalence of OH was higher in MCI and highest in dementia, particularly in VaD and DLB. DPOH, more likely associated with autonomic dysfunction, is a risk factor for incident MCI or dementia.
| S-EPMC6839486 | biostudies-literature
Project description:ObjectiveTo examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up.MethodsWe analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987-1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013. Scores were summarized and reported as SDs. We used adjusted Cox regression and linear mixed models.ResultsOver ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20-1.97) and ischemic stroke (HR 2.08, 95% CI 1.65-2.62). Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 0.09, 95% CI -0.02 to 0.21).ConclusionsOH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.
| S-EPMC6107267 | biostudies-literature
Project description:Take Home Message Use of anticholinergic medication for overactive bladder (OAB) was not associated with a significant decline in markers of cognitive function among a group of individuals with normal or impaired cognition. APOE ε4 allele status did not modify the effect of OAB anticholinergic medications on cognition. Background Few studies have addressed whether anticholinergic (AC) medications for overactive bladder (OAB) cause cognitive decline in individuals with existing cognitive impairment, and whether the APOE ε4 gene increases this risk. Objective To determine whether OAB AC use is associated with a clinically relevant change in cognitive measures among adults with normal and abnormal cognition. Design, setting, and participants This was a retrospective cohort study using data from the National Alzheimer’s Coordinating Center. Patients were enrolled at specialized centers in the USA between 2005 and 2019. Patients with existing OAB AC use, missing APOE ε4 status, and confounding neurologic diagnoses were excluded. New users of an OAB AC were matched 1:1 to patients not taking an OAB AC using propensity scores. Intervention New use of oxybutynin, tolterodine, solifenacin, trospium, darifenacin, or fesoterodine. Outcome measurements and statistical analysis The outcome was a change in cognitive function, measured as a ≥1-point increase on the Clinical Dementia Rating (CDR) instrument or a ≥3-point decrease on the Mini-Mental State Examination (MMSE). Conditional logistic regression with odds ratios (ORs) was conducted. We also tested for APOE ε4 effect modification. Results and limitations Among 18 835 eligible patients, 782 matched pairs were identified. The most common OAB ACs were oxybutynin (38%) and tolterodine (23%). There was no significant increase in the risk of a clinically relevant cognitive decline among OAB AC users (CDR: OR 1.38, 95% confidence interval [CI] 0.93–2.05; p = 0.11, MMSE: OR 1.06, 95% CI 0.79–1.43; p = 0.70). There was no significant interaction between APOE ε4 status and OAB AC use for the CDR (p = 0.38) or MMSE (p = 0.95) outcomes. Users of oxybutynin or tolterodine had numerically higher odds of a change on the CDR test (OR 1.65, 95% CI 0.98–2.77) that was close to statistical significance (p = 0.06). Limitations include the inability to determine medication dose or duration, and residual confounding. Conclusions OAB AC use was not associated with a significant change in cognitive function among individuals with normal and abnormal cognition. Further research is necessary to determine if oxybutynin and tolterodine are significantly more likely to cause cognitive decline. Patient summary Use of a specific class of overactive bladder medication was not associated with negative changes in brain function among patients with either normal or abnormal function. A genetic risk factor for Alzheimer’s disease did not predispose individuals to cognitive decline when taking these drugs. Two of the drugs (oxybutynin and tolterodine) may lead to a higher risk of cognitive decline in comparison to other drugs, and this needs further research.
| S-EPMC9732452 | biostudies-literature
Project description:BackgroundLeukotriene receptor antagonists (LTRAs) alleviate Alzheimer's disease (AD) pathology and improve cognition in animal models; however, clinical evidence is limited. This study aimed to explore the associations between the use of LTRAs (montelukast or zafirlukast) and cognitive performance in people with normal cognition, mild cognitive impairment (MCI), or AD dementia. We hypothesized that LTRA use would be associated with better cognitive performance over time.MethodsThis longitudinal observational study used data from the National Alzheimer's Coordinating Center. Within groups of participants with normal cognition, MCI, or AD dementia, LTRA users were matched 1:3 to non-users using propensity score matching. Cognitive domains including immediate and delayed memory (Wechsler Memory Scale Revised-Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol Substitution Test), and language (animal naming, vegetable naming, and Boston Naming Test) were compared between users and non-users in mixed-effects linear or Poisson regression models.ResultsIn AD dementia, LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol Substitution Test (Β = 1.466 [0.253, 2.678] symbols/year, n = 442), and language, as measured by animal naming (Β = 0.541 [0.215, 0.866] animals/year, n = 566), vegetable naming (B = 0.309 [0.056, 0.561] vegetables/year, n = 565), and the Boston Naming Test (B = 0.529 [0.005, 1.053] items/year, n = 561). Effect sizes were small but persisted after controlling for a 10% false discovery rate. LTRA use was not associated with changes in memory performance in AD, nor was it associated with changes in cognitive performance in people with normal cognition or MCI. In a post hoc analysis, LTRA use was associated with a slower decline in clinical progression in MCI (B = -0.200 [-0.380, -0.019] points/year, n = 800) and AD dementia (B = -0.321 [-0.597, -0.046] points/year, n = 604) as measured by CDR Sum of Boxes.ConclusionsThe use of LTRAs was associated with preserved function in non-amnestic cognitive domains in AD dementia. The role of leukotrienes and their receptors in cognitive decline warrants further investigation and the leukotriene pathway may represent a target for AD treatment.
| S-EPMC8418104 | biostudies-literature
Project description:ObjectiveTo investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design.MethodsIndividuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture.ResultsThe PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function.ConclusionsCognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance.
| S-EPMC5200856 | biostudies-literature
Project description:AimsSystematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall.Method and resultsParticipants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical orthostatic hypotension with symptoms (SOH) was defined as a fall <OH but with unsteadiness, light-headedness, or faintness in the week before blood pressure measurement. Proportional hazard regression was used to examine the relationship between baseline OH, SOH, and cognitive outcomes. There were 3121 in the analytical sample, 538 with OH. Orthostatic hypotension was associated with increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (95% confidence interval 1.14-1.59). For incident dementia (241 events), HR 1.34 (0.98-1.84). When competing risk of cardiovascular events were taken into account results were HR 1.39 (1.19-1.62) and HR 1.34 (1.05-1.73), respectively. Subclinical orthostatic hypotension was associated with an increased risk of cognitive decline HR 1.56 (1.12-2.17) and dementia HR 1.79 (1.00-3.20). Combining the results from the HYVET cohort in a meta-analysis with the existing published literature in this area found a 21% (9-35%) increased risk of dementia with OH.ConclusionOrthostatic hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition.
| S-EPMC6122132 | biostudies-literature
Project description:ObjectivesThis study examined the differences in brain volume and cortical thickness among individuals with normal cognition (NC) and those with NCDs, including mild cognitive impairment (MCI) and dementia. The aim was to identify the brain parameters supporting clinical decision-making for NCDs.MethodA total of 116 participants were categorized into dementia, MCI, and NC groups, and their brain scans using structural magnetic resonance imaging (MRI) were processed and automatedly analyzed with FreeSurfer to obtain the absolute brain volume, volume normalized by intracranial volume (ICV), and cortical thickness. Patients with dementia exhibited a significantly smaller brain volume and cortical thickness than the MCI and NC groups.ResultsThe left amygdala/ICV ratio demonstrated excellent performance in diagnosing early NCDs, with a cutpoint of ≤0.089, providing 83.30% sensitivity, 84.20% specificity, and 83.82% accuracy. For MCI, a cutpoint of ≤0.099 for the left amygdala/ICV yielded 96.70% sensitivity, 83.30% specificity, and 88.46% accuracy.ConclusionsThe findings suggested that reductions in brain volume and cortical thickness correlate with cognitive decline. Utilizing FreeSurfer and MRI data, particularly the left amygdala/ICV ratio, may serve as a valuable biomarker for the early identification of individuals at risk for developing NCDs.
| S-EPMC11852455 | biostudies-literature
Project description:BACKGROUND:Alzheimer's Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. OBJECTIVE:To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. METHODS:Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. RESULTS:Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. CONCLUSION:Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.
| S-EPMC6156780 | biostudies-literature
Project description:IntroductionProgression to Alzheimer's disease (AD) dementia from normal cognition (NC) can follow different trajectories, with most progressing through a recognizable mild cognitive impairment stage (NC-MCI-AD), while some individuals transition quickly from NC to AD dementia (NC-AD).MethodsWe compared demographic characteristics, health factors, and cognitive and functional assessments across three time points: the first NC visit, the last NC visit, and the first AD dementia visit.ResultsThe NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis, despite maintaining better cognitive function during the NC stage. Analysis of yearly changes revealed negligible differences during NC. However, the yearly change during the AD dementia stage suggested potentially more rapid functional decline in the NC-AD group.DiscussionThese findings highlight the heterogeneity in AD disease progression and emphasize the importance of considering diverse progression patterns in AD research and clinical practice.HighlightsWe investigated the disease progression difference between patients who converted to Alzheimer's disease (AD) dementia from normal cognition (NC) directly or through the mild cognitive impairment (MCI) stage. We found that the NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis. We discovered that the NC-AD group had rapid functional decline once patients were confirmed with AD onset.
| S-EPMC11772698 | biostudies-literature
Project description:BackgroundAlthough patient participation in treatment decisions is important for preference-concordant care delivery, it is largely unknown how cognitive impairment influences treatment preferences. We investigated whether treatment preferences for the care of serious illness differ between adults with and without cognitive impairment in hypothetical clinical scenarios.MethodsData from the 2018 Health and Retirement Study were used. The sample included 1291 self-respondents (201 respondents with cognitive impairment, and 1090 with normal cognition). We examined treatment preferences for life-extending, limited, and comfort care options in two hypothetical clinical scenarios where the respondent imagines a patient with (1) good physical health with severe cognitive impairment consistent with dementia; and (2) with physical impairment due to a heart attack, but normal cognition. Respondents specified whether they were unsure, or if they would want or not want each treatment option. Linear probability models were used to compare treatment preferences by cognitive status.ResultsRespondents with cognitive impairment were more likely to report that they were unsure about treatment options across both clinical scenarios compared to those with normal cognition. For the limited treatment option, cognitive impairment was associated with a lower rate of expressing a treatment preference by 7.3 (p = 0.070) and 8.5 (p = 0.035) percentage points for dementia and heart attack scenarios, respectively. Among those who articulated preferences, cognitive impairment was associated with a higher rate of preference for life-extending treatment in both dementia (30.1% vs. 20.0%, p = 0.044) and heart attack scenarios (30.0% vs. 20.2%, p = 0.033).ConclusionsCompared to those with normal cognition, cognitive impairment was associated with greater uncertainty about treatment preferences and higher rates of aggressive care preferences among those who specified preferences. Further research should assess whether preferences for aggressive care become more common as cognition declines in order to improve preference-concordant care delivery for patients with cognitive impairment.
| S-EPMC9772047 | biostudies-literature