Current Aging Science (v.10, #2)

Meet Our Editorial Board Member by Yuri B. Yurov (79-79).

Understanding the molecular mechanism of aging is of utmost importance to the scientific communities. To date, various theories have been proposed and many of them were evaluated as potential targets in the battle against aging. MicroRNAs, the universal gene expression regulators, were found to be associated with the aging process as many of them have been linked to biological process associated with cellular deterioration. In this short report, we briefly review the contribution of miRNAs to the aging process and offer an opinion as to how the knowledge of the role of these molecules in aging can be utilized.

Macronutrient Intake and Distribution in the Etiology, Prevention and Treatment of Osteosarcopenic Obesity by Owen J. Kelly, Jennifer C. Gilman, Youjin Kim, Jasminka Z. Ilich (83-105).
Background: Osteosarcopenic obesity, the combined deterioration of bone, muscle and fat tissues, could become the ultimate trajectory of aging. Aging stem cells are deregulated by low-grade chronic inflammation and possibly by diet. The metabolic shift of stem cells towards adipogenesis results in osteo obesity, sarco obesity and obesity. Macronutrients have numerous physiological functions but are regarded mainly for their energy contribution. Currently, no nutritional causes or treatment/prevention guidelines exist for osteosarcopenic obesity.

Objective: The aim of this review is to assemble the evidence to elucidate if the macronutrient composition of the Western diet has an effect on the development of osteosarcopenic obesity. In view of the role of brain in locomotion a section examining the macronutrients as possible modulators of brain functioning was included.

Method: An extensive literature search of PubMed and Medline was conducted for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and energy, carbohydrate, protein and lipid, and brain. US National Health and Nutrition Examination Survey (NHANES) food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis.

Results: NHANES data showed that energy imbalances in aging, excess high glycemic carbohydrate, lower protein intakes and low long chain polyunsaturated fat intakes may contribute to osteosarcopenic obesity. 135 articles were included in the review.

Conclusion: Early humans probably consumed a diet closer to what the human body was designed for; however, we do not know the ideal energy and macronutrient proportions for optimal health or for preventing/treating aging and osteosarcopenic obesity.


Background: Body composition changes occur with aging; bone and muscle mass decrease while fat mass increases. The collective term for these changes is osteosarcopenic obesity. It is known that conventional resistance exercise programs build/maintain lean mass and reduce fat mass. However, unconventional (to Western society/medicine) forms of exercise may be viable for the treatment/prevention of osteosarcopenic obesity.

Objective: The purpose of this review is to assess relatively unconventional exercises for their efficacy in maintaining/improving bone and muscle mass and reducing fat mass.

Method: A literature search for unconventional exercise showed Tai Chi, yoga, Pilates, whole body vibration, electrical stimulation of muscle, and the Alexander Technique were considered alternative/ unconventional. A PubMed and Medline search for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each exercise was then conducted.

Results: Tai Chi, yoga, and Pilates, in addition to whole body vibration, electrical stimulation of muscle, and the Alexander Technique are all considered low impact. Tai Chi, yoga, and Pilates not only physically support the body, but also increase balance and quality of life. The devices showed promise in reducing or preventing muscle atrophy in older people that are unable to perform conventional exercises.

Conclusion: Any exercise, conventional or otherwise, especially in sedentary older people, at risk of, or diagnosed with osteosarcopenic obesity may be better than none. Exercise prescriptions should suit the patient and the desired outcomes; the patient should not be forced to fit an exercise prescription, so all potential forms of exercise should be considered.


Consciousness, Functional Networks and Delirium Screening by Eamonn Eeles, Hana Burianova, Shaun Pandy, Donna Pinsker (122-128).
Background: Consciousness, the medium of sentient thought, requires integrity of functional networks and their connectivity. In health, they function as a co-operative but mutually exclusive paradigm of introspection versus external awareness subserved via the Default Mode Network and Task Positive State, respectively. Higher thinking in the conscious state is then segregated according to need. There is research evidence to suggest that functional networks may be impacted in disorders of consciousness and conceptual support for a mechanistic role in delirium. This potentially central aspect of delirium manifestation is relatively unexplored.

Objective: This article describes the role of disrupted functional networks in delirium. How this relates to current understanding of delirium neurobiology and the ramifications for clinical diagnosis is discussed.

Method: A review of the role of functional networks, particularly DMN and TPN, has been undertaken with respect to health and delirium. An exploration of how symptoms of delirium may be related to functional network aberrancy has been undertaken. Implications for research and clinical practice in delirium have been presented.

Results: In delirium, a disturbance of consciousness, the DMN is pathologically co-activated and functional cortical connectivity is compromised. The clinical correlate is of an experiential singularity where internal and external drivers become indistinguishable, reality and delusion merge and the notion of self is effaced. Our group propose that functional network disruption in conjunction with cortical disconnectivity is central to the mechanism of delirium. Clinical tools may exploit the neurobiology of delirium to improve its diagnosis and an example of such a simple screening instrument (SQeeC) is provided.

Conclusion: Functional networks are critically disrupted in delirium and may be central to clinical features. A better understanding of the neurobiology of delirium will generate research opportunities with potential for therapeutic gains in detection, diagnosis, and management.


Factors of Rapid Cognitive Decline in Late Onset Alzheimer';s Disease by Pierre Koskas, Marie Cecile Henry-Feugeas, Jean-Paul Feugeas, Phalla Ou, Olivier Drunat (129-135).
Background: Rapid Cognitive Decline (RCD) in Alzheimer's Disease (AD) is associated with a worse disease progression. There is no consensual predictor of RCD and only a few studies have focused on RCD in late-onset dementia, the most common form of AD.

Objective: To identify the predictors of RCD, in a population of community-dwelling patients with recently diagnosed late onset AD.

Methods: Community-dwelling subjects aged >75 consulting for the first time in Old Age Memory outpatient center from 2009 to 2012 were considered. All patients underwent a standardized clinical dementia investigation. Patients were classified as rapid decliners when they demonstrated a loss of 3 points or greater in MMSE during the first six months.

Results: 130 patients were included (42 males, 88 females, mean ages 82.7±4.58). The average baseline MMSE score was 23.36±3.78. In regression analysis, the Free Recall Scores, categorical fluency scores were the most highly predictive of RCD.

Conclusion: These results are important for the design of clinical trials and also, in clinical practice, for both physicians and families in planning long-term care.


Early and Mild Phases of Primary Progressive Aphasia: A Case Series by Jessica Powell, James Lendrum, Rosalind Huff, Christine Belden, Marwan N. Sabbagh (136-142).
Background: The early and mild phases of various neurodegenerative diseases, sometimes described as Mild Cognitive Impairment (MCI), has been characterized as the transitional state between normal cognition and dementia. It is described as having cognitive decline not severe enough to cause functional impairment. MCI has been divided into amnestic and non-amnestic subtypes with the amnestic subtype most commonly progressing to AD. The MCI phase of other dementias such as DLB has also been described. There are very few reports summarizing this early phase of Primary Progressive Aphasia.

Aims: Our aim is to contribute to the clinical characterization of the early and mild phases of clinically suspect PPA in order to better describe the presenting features and neuropsychological profile.

Methods: This is a cross-sectional case series abstracted from our memory disorders clinic. We retrospectively queried and analyzed the cases of 9 patients with a primary diagnosis of MCI and secondary diagnosis of progressive aphasia. Acquired (non-degenerative) aphasias (e.g. stroke, mass) were excluded.

Results: Of the 9 cases, 5 were non-amnestic MCI and 4 were amnestic MCI, all with language as the primary domain. All eMCI cases were non-amnestic. Word finding difficulty was observed in 8 of the 9 cases and sentence repetition impairments in 8 of 8 tested.

Conclusion: PPA is a syndrome with an underlying progressive neurodegenerative etiology that results in dementia. PPA, like other neurodegenerative conditions, can transition through an early (i.e. MCI) phase prior to the dementia phase. The clinical description of this early stage of PPA is predominantly characterized by word finding difficulty on observation, sentence repetition impairment on neuropsychological testing, and a diagnosis of MCI or early MCI (eMCI) with language as the primary impaired domain ± an amnestic component.


Background: Hyponatraemia has been associated with increased falls risk. However, this has not been adequately investigated in the context of In-Hospital Falls (IHFs).

Objectives: To determine the potential risk factors for IHFs, particularly the role of hyponatraemia.

Methods: Patients aged >65 years with an incident IHF during admissions under a General Internal Medicine (GIM) Unit over six months were studied. For each case, two age and sex matched controls were randomly selected from patients who were admitted under the GIM unit during the same time as the cases. The relevant data were obtained by review of medical records.

Results: The prevalence of IHF was 7.2%. Hyponatraemia had a significant univariate association with IHF (P=0.005). This association remained significant even after controlling the covariates (adjusted odds ratio (OR) 1.890, 95% confidence interval (CI) 1.391-3.497, P=0.021). The frequency of IHF did not vary with the severity of hyponatraemia (P=0.267). The other variables that had an independent association with IHFs were admission falls (OR 1.570, CI 1.340-5.833, P=0.030), use of psychotropic medications (OR=4.440, CI 2.051-13.240, P<0.001) and diuretics (OR=0.827, CI 0.767-0.901, P=0.010), and cardiovascular diagnosis (OR=0.916, CI 0.893-0.942, P=0.039).

Conclusion: Hyponatraemia has an independent association with increased risk of IHFs. Other potential risk factors for IHFs include admission falls and psychotropic medication use. Diuretic use and cardiovascular diagnosis have a significant inverse association with IHFs.


Comprehensive Assessment of Compliance with Antimuscarinic Drug Treatment in the Case of Urge Urinary Incontinence of Older Patients by Kirill V. Kosilov, Sergey A. Loparev, Irina G. Kuzina, Olga V. Shakirova, Natalya S. Zhuravskaya, Alexandra Lobodenko (149-156).
Aim: To investigate the heterogeneous factors affecting the stability of patients older than 60 years in the UI treatment with Antimuscarinics.

Background: The prevalence of Urge Incontinence (UI) in older persons reaches 29.3%. The symptoms of urinary incontinence in older people reduce the health related life quality.

Materials and Methods: In 1257 patients over 60 years (857 (68.2%) women - average age 67.8, 400 (31.8%) men - 71.4), who received AM for one year, demographic, socio-economic and health parameters were studied. OABq-SF questionnaires, MOS SF-36, urination diaries, uroflowmetry, income information from the tax offices and outpatient records were used.

Result: The compliance to AM treatment within 6 months was retained in 44.2%, and within the year - 26.8% of older patients. At least 40% of the total number of patients refused to continue the treatment for medical reasons. The persons taking Solifenacin (p≤ 0.01), Trospium (p≤ 0.05), or Darifenacin (p≤ 0.05), suffering from severe UI symptoms (p≤ 0.01), and experiencing minor side effects (p≤ 0.01), well-informed about UI treatment methods (p≤ 0.01) prevailed among the treatment compliant patients. At least 20.4% of the patients discontinued their treatment due to economic reasons. The persons with significantly larger annual income (p≤ 0.05) and annual medical cost (p≤ 0.01) prevailed among the treatment compliant patients. About 12.2% of the patients stopped their treatment for reasons related to the social background and psychological status.

Conclusion: In this experiment, we found that AM treatment compliance in older patients, in addition to medical parameters and health conditions, is largely affected by the economic as well as social, demographic and psychological factors. The study results can be claimed by practitioners involved in correcting UI symptoms in older people.