New horizons in the diagnosis and management of Alzheimer's Disease in older adults.

Alzheimer's Disease (ad) is the most common cause of dementia, and in addition to cognitive decline, it directly contributes to physical frailty, falls, incontinence, institutionalisation and polypharmacy in older adults. Increasing availability of clinically validated biomarkers including cerebrospinal fluid and positron emission tomography to assess both amyloid and tau pathology has led to a reconceptualisation of ad as a clinical-biological diagnosis, rather than one based purely on clinical phenotype. However, co-pathology is frequent in older adults which influence the accuracy of biomarker interpretation. Importantly, some older adults with positive amyloid or tau pathological biomarkers may never experience cognitive impairment or dementia. These strides towards achieving an accurate clinical-biological diagnosis are occurring alongside recent positive phase 3 trial results reporting statistically significant effects of anti-amyloid Disease-Modifying Therapies (DMTs) on disease severity in early ad. However, the real-world clinical benefit of these DMTs is not clear and concerns remain regarding how trial results will translate to real-world clinical populations, potential adverse effects (including amyloid-related imaging abnormalities), which can be severe and healthcare systems readiness to afford and deliver potential DMTs to appropriate populations. Here, we review recent advances in both clinical-biological diagnostic classification and future treatment in older adults living with ad. Advocating for access to both more accurate clinical-biological diagnosis and potential DMTs must be done so in a holistic and gerontologically attuned fashion, with geriatricians advocating for enhanced multi-component and multi-disciplinary care for all older adults with ad. This includes those across the ad severity spectrum including older adults potentially ineligible for emerging DMTs.

Therapeutic dilemmas: cognitive enhancers and risk of falling in older adults-a clinical review.

PURPOSE: Cognitive enhancers are the primary pharmacological therapy prescribed to those with dementia, comprising of memantine and the acetylcholinesterase inhibitors (AChEIs). The long-term cognitive and behavioural benefits of these medications, as well as their potential contribution to falls is currently debated, with recent Delphi studies being unable to reach consensus on whether these medications should be deprescribed. In this narrative clinical review, as part of a series on deprescribing in people at risk of falls, we explore the potential falls-related side effects experienced in people taking cognitive enhancers, alongside situations where deprescribing may be appropriate. METHODS: We undertook a literature search of PubMed and Google Scholar, using terms capturing falls and cognitive enhancers, as well as consulting the British National Formulary and published Summary of Medicinal Product Characteristics. These searches informed the subsequent clinical review. RESULTS: Cognitive enhancers should be subject to regular review, including confirmation of appropriate treatment indication, and occurrence of side effects in the context of falls. AChEIs, in particular, are associated with a broad range of side effects that can contribute to increased falls risk. These include bradycardia, syncope and neuromuscular effects. Where these have been identified, deprescribing should be considered, as well as alternative treatment options. Deprescribing studies have shown mixed results, likely due to considerable methodological heterogeneity. Several suggested guidelines exist to aid deprescribing decisions, many of which are highlighted in this review. CONCLUSIONS: The use of cognitive enhancers should be regularly reviewed and decisions to deprescribe made on a case-by-case basis, considering both the risks and benefits of stopping these medications.

The treatment of hypertension in people with dementia: a systematic review of observational studies.

BACKGROUND: Hypertension is very common in older people and a number of trials of antihypertensives have demonstrated benefit from treatment in even the oldest old. However, people with dementia were significantly under-represented in these studies and as a population are more likely to be physically frail, to suffer orthostatic hypotension and to experience adverse effects from polypharmacy at a lower drug count. It may be that different thresholds for commencement and cessation of treatment should be considered and may already be used for this group. Against this background this review sets out to describe the prevalence of hypertension in people with dementia, its treatment, change in treatment over time and the achievement of blood pressure (BP) control. METHODS: The PubMed, Cochrane, Embase and PsychINFO databases were searched for observational studies involving people with dementia and a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onwards. Abstracts and titles were then reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analysed and appraised. RESULTS: Thirteen articles were identified for analysis. The prevalence of hypertension in people with dementia was 45% (range 35%-84%). 73% of these were on at least one antihypertensive, with diuretics being the most common. The reported prevalence of hypertension in study populations remained unchanged over time. ACEi/ARBs and calcium channel blockers were prescribed more frequently in more recent studies whilst use of ß-blockers and diuretics remained unchanged. Target blood pressure was achieved in 55% of those on treatment. CONCLUSION: Hypertension is as common in people with dementia as in other populations and is as commonly treated with antihypertensive drugs. The findings presented here will support further work to establish the risk-benefit of antihypertensive treatment in patients with dementia and, if differing ratios are identified, to establish dementia-specific guidelines for management.

The treatment of hypertension in care home residents: a systematic review of observational studies.

AIM: To describe the prevalence of hypertension in care home residents, its treatment, change in treatment over time, and the achievement of blood pressure (BP) control. METHOD: The PubMed, Cochrane, Embase, and PsychINFO databases were searched for observational studies involving care home residents with a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onward. Abstracts and titles were reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analyzed and appraised. RESULTS: Sixteen articles were identified for analysis, of which half were studies carried out in the United States. The prevalence of hypertension in care home residents was 35% (range 16%-71%); 72% of these were on at least 1 antihypertensive (mean 1.5 antihypertensives per individual), with diuretics being the most common. The prevalence of hypertension in study populations was greater in more recent studies (P = .004). ACEi/ARBs (P = .001) and ß-blockers (P = .04) were prescribed more frequently in recent studies, whereas use of calcium-channel blockers and diuretics remained unchanged over time. The number of antihypertensives prescribed per patient was higher (correlation 0.332, P = .009), whereas fewer patients achieved target BP (correlation -0.671, P = .099) in more recent studies. CONCLUSION: Hypertension is common in care home residents and is commonly treated with antihypertensive drugs, which were prescribed more frequently in more recent studies but with no better BP control. These studies indicate a tendency toward increasing polypharmacy over time, with associated risk of adverse events, without demonstrable benefit in terms of BP control.

Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer.

PURPOSE: The role played by the innate immune system in determining survival from non-small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC. METHODS: We used immunohistochemistry to identify tryptase+ mast cells and CD68+ macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC. RESULTS: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7.7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection. CONCLUSION: The tumor islet CD68+ macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study.