Sean Kennelly

Blood pressure and the risk for dementia—A double edged sword

Alzheimers disease (AD) and vascular dementia (VaD) are important causes of cognitive decline in the elderly. As a result of the aging population, the incidence of dementia is expected to increase substantially over the coming decades. Many studies have identified that vascular risk factors are implicated in the pathogenesis of both AD and VaD. Longitudinal studies have suggested that high blood pressure in midlife is associated with a higher incidence of both AD and VaD in later life. The association appears weaker for hypertension in later life. Some studies also suggest that hypotension; especially low diastolic blood pressure in late-life is also associated with an increased risk of AD. Long-standing hypertension may lead to severe atherosclerosis and impaired cerebrovascular autoregulation. A decline in blood pressure in later life may contribute to diminished cerebral perfusion. The subsequent ischaemic state may lead to increased cerebral beta-amyloid accumulation.

Review: Blood pressure and dementia — a comprehensive review

Alzheimers disease (AD) and vascular dementia (VaD) are important causes of cognitive decline in the elderly. As a result of an ageing population worldwide, the incidence of dementia is expected to rise exponentially over the coming decades. Vascular risk factors are implicated in the pathogenesis of both AD and VaD. Hypertension in midlife is particularly associated with an increased risk of developing dementia. One might hope the treatment of high blood pressure in midlife would reduce the risk of developing dementia, as it does the risk of stroke. Divergent results have been reported in studies examining this effect, with the evidence suggesting that certain antihypertensives confer benefits beyond others. This implies that certain drugs may have neuroprotective properties separate to their blood pressure lowering capabilities. Recent trials have added to our understanding of these relationships.

Knowledge, skills and attitudes of doctors towards assessing cognition in older patients in the emergency department.

Purpose of the study Although cognitive impairment and delirium are highly prevalent in older patients who present to the emergency department, multiple studies have highlighted inadequate detection by doctors. This study investigated potential reasons underlying this. Study Design A 14-item self-administered questionnaire was distributed to all medical, surgical and emergency department physicians involved in the care of older patients in the emergency department of an urban university teaching hospital between January and March 2012. Results The questionnaire was completed by 76/97 (78%) of eligible respondents. Respondents reported screening an average of one in four older patients that they reviewed. Almost one-third (22/76, 29%) felt they lacked the relevant expertise to perform cognitive screening: those with training in geriatrics were less likely to cite lack of expertise as a factor. While the majority felt screening for cognition in the emergency department-setting was important (59/76, 78%), several limiting factors were identified: lack of a screening tool; lack of privacy; too much noise; and time constraints. There was no consensus on who should perform screening. Conclusions Doctors reviewing patients in the emergency department-setting reported several important factors limiting their ability to screen older patients for cognitive impairment. Respondents to this questionnaire did not feel the emergency department environment was conducive towards the assessment of cognition in older patients. Clarification of each disciplines responsibility in the detection, assessment and management of delirium and/or dementia, and the implementation of emergency department cognitive screening instruments more suited to this setting would likely improve detection and management.

Demonstration of safety in Alzheimer's patients for intervention with an anti-hypertensive drug Nilvadipine: results from a 6-week open label study

Nilvadipine may lower rates of conversion from mild‐cognitive impairment to Alzheimers disease (AD), in hypertensive patients. However, it remains to be determined whether treatment with nilvadipine is safe in AD patients, given the higher incidence of orthostatic hypotension (OH) in this population, who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP.

Apolipoprotein E genotype‐specific short‐term cognitive benefits of treatment with the antihypertensive nilvadipine in Alzheimer's patients—an open‐label trial

Evidence suggests that dihydropyridine calcium channel blockers may be useful in preventing and treating Alzheimers disease (AD).

Walking the cognitive "minefield" between high and low blood pressure.

Vascular risk factors are implicated in the pathogenesis of Alzheimers disease (AD). There is an age-dependent relationship between blood pressure and the risk of AD. Given the potential temporal lag that can exist between the two conditions, longitudinal population studies offer the best opportunity to identify a causal relationship. Midlife hypertension increases the risk for AD, yet later-life hypertension does not appear to confer the same risk and may in fact be protective. Low diastolic blood pressure, especially in later-life, is associated with an increased risk of AD. Orthostatic hypotension and other neurocardiovascular syndromes may increase the risk for cognitive impairment and AD. Several physiopathological mechanisms may contribute to this increased risk. Dynamic blood pressure changes and impaired cerebrovascular autoregulation may result in cerebral hypoperfusion. Hypertensive patients also develop cerebral infarcts, resulting in diminished perfusion. Subsequent hypoxia driven pathways result in increased cerebral amyloid-β and phosphorylated tau protein accumulation. Treatment of elevated blood pressure with antihypertensive medications attenuates the risk of AD attributable to elevated midlife hypertension. Certain antihypertensive compounds have neuroprotective properties that may reduce the risk of AD, independent of their effects on blood pressure.

Drug treatments in Alzheimer’s disease

Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimers disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy.

Characteristics and outcomes of older persons attending the emergency department: a retrospective cohort study

BACKGROUND The analysis of routinely collected hospital data informs the design of specialist services for at-risk older people. AIM Describe the outcomes of a cohort of older emergency department (ED) attendees and identify predictors of these outcomes. DESIGN retrospective cohort study. METHODS All patients aged 65 years or older attending an urban university hospital ED in January 2012 were included (N = 550). Outcomes were retrospectively followed for 12 months. Statistical analyses were based on multivariate binary logistic regression models and classification trees. RESULTS Of N = 550, 40.5% spent ≤6 h in the ED, but the proportion was 22.4% among those older than 81 years and not presenting with musculoskeletal problems/fractures. N = 349 (63.5%) were admitted from the ED. A significant multivariate predictor of in-hospital mortality was Charlson comorbidity index [CCI; odds ratio = 1.19, 95% confidence interval: 1.07, 1.34, P = 0.002]. Among patients who were discharged from ED without admission or after their first in-patient admission (N = 499), 232 (46.5%) re-attended ED within 1 year, with CCI being the best predictor of re-attendance (CCI ≤ 4: 25.8%, CCI > 5: 60.4%). Among N = 499, 34 (6.8%) had died after 1 year of initial ED presentation. The subgroup (N = 114) with the highest mortality (17.5%) was composed by those aged >77 years and brought in by ambulance on initial presentation. CONCLUSIONS Advanced age and comorbidity are important drivers of outcomes among older ED attendees. There is a need to embed specialist geriatric services within frontline services to make them more gerontologically attuned. Our results predate the opening of an acute medical unit with specialist geriatric input.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

Introduction This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimers disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimers disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimers disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. Trial registration number EUDRACT Reference Number: 2012-002764-27.

Dementia in the acute hospital: the prevalence and clinical outcomes of acutely unwell patients with dementia

Background: Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. Aim: To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. Design: Prospective observational study. Methods: 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. Results: Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. Conclusion: A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment.