Lucidity in dementia: A perspective from the NIA.

In this issue of Alzheimer's & Dementia, Mashour et al. propose the intriguing hypothesis that some manifestations of late-stage dementia are reversible, albeit transiently. Calling this phenomenon paradoxical lucidity, their paper follows a 2018 workshop sponsored by the National Institute on Aging that assessed the state of knowledge on lucidity in dementia and identified areas ripe for further study.

Interventions to improve the quality of life and survivorship of older adults with cancer: The funding landscape at NIH, ACS and PCORI.

Identifying knowledge gaps and research opportunities in cancer and aging research was the focus of a three-part conference series led by the Cancer and Aging Research Group from 2010 to 2015. The third meeting, featured representatives from the NIA, NCI, ACS and PCORI each of whom discussed research priorities and funding opportunities in cancer and aging at their respective agencies. This manuscript reports on the proceedings of that conference with a specific focus on funding priorities for interventions to improve the quality of life and survivorship of older adults with cancer.

Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events.

Biological, clinical, and psychosocial correlates at the interface of cancer and aging research.

In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: (1) improved standardized geriatric assessment of older oncology patients, (2) substantially enhanced biological assessment of older oncology patients, (3) specific trials for the most vulnerable and/or those older than 75 years, and (4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations.

Improving the pharmacologic management of pain in older adults: identifying the research gaps and methods to address them.

Objective: There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits.

Acute kidney injury in older adults.

Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late.

Workshop on idiopathic pulmonary fibrosis in older adults.

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments.

Bedside-to-Bench conference: research agenda for idiopathic fatigue and aging.

The American Geriatrics Society, with support from the National Institute on Aging and the John A. Hartford Foundation, held its fifth Bedside-to-Bench research conference, "Idiopathic Fatigue and Aging," to provide participants with opportunities to learn about cutting-edge research developments, draft recommendations for future research, and network with colleagues and leaders in the field. Fatigue is a symptom that older persons, especially by those with chronic diseases, frequently experience.

Fatigue and fatigability in older adults.

Fatigue is believed to be a common complaint among older adults; however, multiple studies of self-reported fatigue across the lifespan have found this may not be the case. To explain this paradox, this article considers "fatigability"-a phenotype characterized by the relationship between an individual's perceived fatigue and the activity level with which the fatigue is associated. Fatigability may be measured by combining self-report measures of fatigue with performance of physical or cognitive activities, provided that the work of the activity is known or can be standardized.

Toward an integrated research agenda for critical illness in aging.

Aging brings an increased predisposition to critical illness. Patients older than 65 years of age account for approximately half of all intensive care unit (ICU) admissions in the United States, a proportion that is expected to increase considerably with the aging of the population. Emerging research suggests that elderly survivors of intensive care suffer significant long-term sequelae, including accelerated age-related functional decline.

Autoimmune autonomic ganglionopathy: treatment by plasma exchanges and rituximab.

This case report describes successful treatment of autoimmune autonomic ganglionopathy (AAG) in a 74-year-old woman by total plasma exchanges (PLEX) and rituximab. Two series of PLEX temporarily, but dramatically improved orthostatic intolerance and hypotension and baroreflex function, in a manner inversely related to ganglionic neuronal nicotinic receptor antibody titer. After rituximab treatment, the antibody titer was decreased modestly but persistently, and the patient had symptomatic and clinical laboratory evidence of continued benefit for at least 10 months, supporting the autoimmune pathogenesis of AAG.

Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation.

Background: Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baro reflexive modulation of autonomic outflows.

Fatigue in a representative population of older persons and its association with functional impairment, functional limitation, and disability.

Background: Older persons often complain of fatigue, but the functional consequences of this symptom are unclear. The aim of the present study was to evaluate fatigue and its association with measures of physical function and disability in a representative sample of the older population.

Methods: Cross-sectional data from a population-based sample of 1,055 Italian men and women aged 65 and older were analyzed.

Attenuated pre-ejection period response to tyramine in patients with cardiac sympathetic denervation.

Stress is a well-known factor affecting cardiac contractility through the cardiac sympathetic nerves. A positive inotropic effect of the cardiac sympathetic nerves on the myocardium is reflected by pre-ejection period (PEP) shortening. Patients with Parkinson disease (PD) and neurogenic orthostatic hypotension (NOH) (PD + NOH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-[(18)F]Fluorodopamine-derived radioactivity, reflecting cardiac sympathetic denervation.

Functional effects of cardiac sympathetic denervation in neurogenic orthostatic hypotension.

Background: Diseases characterized by neurogenic orthostatic hypotension (NOH), such as Parkinson disease (PD) and pure autonomic failure (PAF), are associated with cardiac sympathetic denervation, as reflected by low myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity. We studied the impact of such denervation on cardiac chronotropic and inotropic function.

Methods: Cardiac inotropic function was assessed by the pre-ejection period index and the systolic time ratio index in response to the directly acting beta-adrenoceptor agonist, isoproterenol, and to the indirectly acting sympathomimetic amine, tyramine, in patients with PD+NOH or PAF (PD+NOH/PAF group, N=13).

Cardiac sympathetic hypo-innervation in familial dysautonomia.

Objective: Familial dysautonomia (FD) involves incomplete development of the sympathetic nervous system. Whether such loss extends to sympathetic innervation of the heart has been unknown. This study used 6-[(18)F]fluorodopamine neuroimaging to assess cardiac sympathetic innervation and function in FD.

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy.

Objective: Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).

Methods: In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2h after 6-[18F]fluorodopa injection, septal myocardial radioactivity measured 8min after 6-[18F]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)).

Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation.

Background: Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baroreflexive modulation of autonomic outflows.

Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes.

Background: Neurogenic orthostatic hypotension (OH) characterizes pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. We used neuropharmacologic probes that might distinguish these diseases based on loss of sympathetic noradrenergic nerves in PAF and PD + OH but not in MSA, and related the results to neurochemical and neuroimaging findings in the same patients.

Methods: Patients with neurogenic OH (PD + OH; N = 35), MSA (N = 41), and PAF (N = 12) received iv trimethaphan (TRI), which inhibits sympathetic nerve traffic, or yohimbine (YOH), which stimulates sympathetic traffic.

Coronary vascular resistance in primary chronic autonomic failure.

Patient groups with chronic autonomic failure and neuroimaging evidence of intact or absent cardiac sympathetic innervation had similar mean values for myocardial perfusion. Cardiac sympathetic outflow does not seem to contribute to coronary vascular resistance.

Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope.

In patients with neurocardiogenic syncope, head-up tilt often evokes acute loss of consciousness accompanied by vasodilatation, increased plasma adrenaline and systemic hypotension. Since hypotension increases adrenaline levels and adrenaline can produce skeletal muscle vasodilatation by activating beta2 receptors, adrenaline might induce a positive feedback loop precipitating circulatory collapse. We hypothesized that propranolol, a non-selective beta-blocker, would prevent adrenaline-induced vasodilatation and thereby prevent syncope.

Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment.

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine).