Late-life Cognitive Disorders Research Articles

Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders.

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.

Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer's Disease.

Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. The current study sought to add to this growing literature. Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.

Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders.

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.

Affective Computing for Late-Life Mood and Cognitive Disorders.

Affective computing (also referred to as artificial emotion intelligence or emotion AI) is the study and development of systems and devices that can recognize, interpret, process, and simulate emotion or other affective phenomena. With the rapid growth in the aging population around the world, affective computing has immense potential to benefit the treatment and care of late-life mood and cognitive disorders. For late-life depression, affective computing ranging from vocal biomarkers to facial expressions to social media behavioral analysis can be used to address inadequacies of current screening and diagnostic approaches, mitigate loneliness and isolation, provide more personalized treatment approaches, and detect risk of suicide. Similarly, for Alzheimer's disease, eye movement analysis, vocal biomarkers, and driving and behavior can provide objective biomarkers for early identification and monitoring, allow more comprehensive understanding of daily life and disease fluctuations, and facilitate an understanding of behavioral and psychological symptoms such as agitation. To optimize the utility of affective computing while mitigating potential risks and ensure responsible development, ethical development of affective computing applications for late-life mood and cognitive disorders is needed.

Oral frailty and neurodegeneration in Alzheimer's disease.

Frailty is a critical intermediate status of the aging process with a multidimensional and multisystem nature and at higher risk for adverse health-related outcomes, including falls, disability, hospitalizations, institutionalization, mortality, dementia, and Alzheimer’s disease. Among different frailty phenotypes, oral frailty has been recently suggested as a novel construct defined as a decrease in oral function with a coexisting decline in cognitive and physical functions. We briefly reviewed existing evidence on operational definitions of oral frailty, assessment and screening tools, and possible relationships among oral frailty, oral microbiota, and Alzheimer’s disease neurodegeneration. Several underlying mechanism may explain the oral health-frailty links including undernutrition, sarcopenia linked to both poor nutrition and frailty, psychosocial factors, and the chronic inflammation typical of oral disease. Oral microbiota may influence Alzheimer’s disease risk through circulatory or neural access to the brain and the interplay with periodontal disease, often causing tooth loss also linked to an increased Alzheimer’s disease risk. On this bases, COR388, a bacterial protease inhibitor targeting Porphyromonas gingivalis implicated in periodontal disease, is now being tested in a double-blind, placebo-controlled Phase II/III study in mild-to-moderate Alzheimer’s disease. Therefore, oral status may be an important contributor to general health, including Alzheimer’s disease and late-life cognitive disorders, suggesting the central role of preventive strategies targeting the novel oral frailty phenotype and including maintenance and improvement of oral function and nutritional status to reduce the burden of both oral dysfunction and frailty.

Mind-Body Interventions in Late-Life Mental Illnesses and Cognitive Disorders: A Narrative Review

Current pharmacological treatments and psychotherapeutic approaches often have adverse effects or are ineffective in late-life cognitive and mental illnesses. Mind-body interventions offer a holistic approach and are of interest because of potential patient acceptability and scalability. To synthesize current evidence on mind-body interventions in treating or preventing mental illnesses and cognitive disorders in older adults. A search was conducted using Ovid MEDLINE, EMBASE, and PsycINFO articles published from 1993 to 2017. 1) Randomized controlled trials, 2) involving older adults (>60 years old), 3) suffering from mental illness or cognitive decline, 4) comparing mind-body interventions with a control group. Mind-body interventions included: imagery, meditation, prayer, autogenic training, tai chi & variants, and yoga. Control group included: health education, other non-pharmacological interventions, treatment as usual, or no treatment at all. Data included number of patients, age, psychiatric diagnoses, type of intervention, frequency andduration, control conditions, outcomes measures and treatment results. 3916 articles were reviewed and ten met inclusion criteria. Six were on Tai Chi and four assessed meditation-based therapies. Clinically significant improvement in depressive and anxiety symptoms were reported, as well as improvement insomedomains of cognition and reduced risk of cognitive deterioration. There is increasing evidence that mind-body interventions may potentially be useful in the treatment or prevention of geriatric mental illnesses and cognitive disorders. There are important methodological limitations of the current literature such as small sample sizes, heterogeneous study populations, and varying clinical outcomes.

Nutritional Intervention as a Preventive Approach for Cognitive-Related Outcomes in Cognitively Healthy Older Adults: A Systematic Review.

The link diet-cognitive function/dementia has been largely investigated in observational studies; however, there was a lack of evidence from randomized clinical trials (RCTs) on the prevention of late-life cognitive disorders though dietary intervention in cognitively healthy older adults. In the present article, we systematically reviewed RCTs published in the last four years (2014-2017) exploring nutritional intervention efficacy in preventing the onset of late-life cognitive disorders and dementia in cognitively healthy subjects aged 60 years and older using different levels of investigation (i.e., dietary pattern changes/medical food/nutraceutical supplementation/multidomain approach and dietary macro- and micronutrient approaches) as well as possible underlying mechanisms of nutritional prevention. From the 35 included RCTs, there was moderate evidence that intervention through dietary pattern changes, medical food/nutraceutical supplementation, and multidomain approach improved specific cognitive domains or cognitive-related blood biomarkers. There was high evidence that protein supplementation improved specific cognitive domains or functional status in prefrail older adults without effect on cognitive function. For fatty acid supplementation, mainly long-chain polyunsaturated fatty acids, there was emerging evidence suggesting an impact of this approach in improving specific cognitive domains, magnetic resonance imaging (MRI) findings, and/or cognitive-related biomarkers also in selected subgroups of older subjects, although some results were conflicting. There was convincing evidence of an impact of non-flavonoid polyphenol and flavonoid supplementations in improving specific cognitive domains and/or MRI findings. Finally, there was only low evidence suggesting efficacy of intervention with homocysteine-related and antioxidant vitamins in improving cognitive functions, dementia incidence, or cognitive-related biomarkers in cognitively healthy older subjects.

Different Cognitive Frailty Models and Health- and Cognitive-related Outcomes in Older Age: From Epidemiology to Prevention

Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre-MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders.

Mind-Body Therapies for Late-Life Mental and Cognitive Health.

A growing body of research supports the use of mind-body therapies (MBTs) as minimally invasive and effective approaches for the management of late-life mood and cognitive disorders. Recent randomized controlled trials and meta-analyses indicate that MBTs are effective for enhancing well-being, mood, sleep, and cognition in older adults. Evidence suggests that mindful movement (e.g., yoga, tai chi, walking meditation) may even outperform conventional physical exercise with regard to effects on quality of life, mood, and cognitive functioning. Practitioners may recommend MBTs as holistic, effective approaches for the management of common late-life mood and cognitive disorders. Continued research on MBTs will inform the development of even more effective/targeted interventions and contribute to greater acceptance and integration of these therapies into geriatric medicine and psychiatry.

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review.

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.

Mobile Health Technology in Late-Life Mental Illness: A Focused Literature Review

In an era of rising geriatric mental health care needs worldwide, technological advances can help address care needs in a cost-effective fashion. Our objective in this review was to assess whether mobile health technology, such as tablets and smartphones, are feasible to use in patients with late-life mental and cognitive disorders, as well as whether they were generally reliable modes of mental health/cognitive assessment. We performed a focused literature review of MEDLINE, PsychInfo, and Embase databases, including papers specifically assessing the implementation of mobile health technologies: electronic tablets (e.g., iPad), smartphones, and other mobile computerized equipment in older adults (age ≥65 years) diagnosed with or at risk of a mental and/or cognitive disorder. A total of 2,079 records were assessed, of which 7 papers were of direct relevance. Studies investigated a broad variety of mobile health technologies. Almost all examined samples with dementia/cognitive dysfunction or at risk for those disorders. All studies exclusively examined the use of mobile health technologies for the assessment of cognitive and or mental illness symptoms or disorders. None of the studies reported participants having any difficulties using the mobile health technology assessments and overall reliability was similar to paper-and-pencil modes of assessment. Overall, mobile health technologies were found to be feasible by patients and had promising reliability for the assessment of cognitive and mental illness domains in older adults. Future clinical trials will be necessary to assess whether portable communication interventions (e.g., symptom tracking) can improve geriatric mental health outcomes.

Complementary and Integrative Therapies for Mental Health and Agingedited by Helen Lavretsky, Martha Sajatovic, and Charles Reynolds III. New York, Oxford University Press, 2016, 592 pp., $125.00 (hardcover).

Complementary and Integrative Therapies for Mental Health and Agingedited by Helen Lavretsky, Martha Sajatovic, and Charles Reynolds III. New York, Oxford University Press, 2016, 592 pp., $125.00 (hardcover).

Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition.

Advancing age is the focus of recent studies on familial and sporadic Alzheimer's disease (AD), suggesting a prolonged pre-clinical phase several decades before the onset of dementia symptoms. Influencing some age-related conditions, such as frailty, may have an impact on the prevention of late-life cognitive disorders. Frailty reflects a nonspecific state of vulnerability and a multi-system physiological change with increased risk for adverse health outcomes in older age. In this systematic review, frailty indexes based on a deficit accumulation model were associated with late life cognitive impairment and decline, incident dementia, and AD. Physical frailty constructs were associated with late-life cognitive impairment and decline, incident AD and mild cognitive impairment, vascular dementia, non-AD dementias, and AD pathology in older persons with and without dementia, thus also proposing cognitive frailty as a new clinical condition with co-existing physical frailty and cognitive impairment in non-demented older subjects. Considering both physical frailty and cognitive impairment as a single complex phenotype may be central in the prevention of dementia and its subtypes with secondary preventive trials on cognitive frail older subjects. The mechanisms underlying the cognitive-frailty link are multi-factorial, and vascular, inflammatory, nutritional, and metabolic influences may be of major relevance. There is a critical need for randomized controlled trials of intervention investigating the role of nutrition and/or physical exercise on cognitive frail subjects with the progression to dementia as primary outcome. These preventive trials and larger longitudinal population-based studies targeting cognitive outcomes could be useful in further understanding the cognitive-frailty interplay in older age.

Targeting Cognitive Frailty: Clinical and Neurobiological Roadmap for a Single Complex Phenotype.

Late-life cognitive disorders may be prevented by influencing age-related conditions such as frailty, characterized by decreased resistance to stressors and increased risk for adverse health outcomes. In the present review article, we examined clinical and epidemiological studies investigating the possible role of different frailty models in modulating the risk of Alzheimer's disease (AD), dementia, vascular dementia (VaD), mild cognitive impairment (MCI), and late-life cognitive impairment/decline that have been published over the past 3 years. Both deficit accumulation and physical frailty models were associated with late-life cognitive impairment/decline, incident dementia, AD, MCI, VaD, non-AD dementias, and AD pathology, proposing cognitive frailty as a new clinical construct with coexisting physical frailty and cognitive impairment in nondemented older subjects. Two subtypes of this new clinical condition have been recently proposed: "potentially reversible" cognitive frailty and "reversible" cognitive frailty. The physical factors should be physical prefrailty and frailty, while the cognitive impairment of potentially reversible cognitive frailty should be MCI (Clinical Dementia rating Scale = 0.5), while the cognitive impairment of reversible cognitive frailty should be pre-MCI Subjective Cognitive Decline (SCD), as recently proposed by the SCD Initiative Working Group. The mechanisms underlying the cognitive-frailty link are multifactorial and vascular, inflammatory, nutritional, and metabolic influences may be of major relevance. Considering both physical frailty and cognition as a single complex phenotype may be crucial in the prevention of dementia and its subtypes with secondary preventive trials on cognitive frail older subjects.

Age-related hearing impairment and frailty in Alzheimer's disease: interconnected associations and mechanisms.

Among potentially modifiable age-related conditions linked to dementia, Alzheimer's disease (AD), and late-life cognitive disorders, age-related hearing impairment (ARHI) or presbycusis is the most widely diffused sensory disorder and one of the principal causes of chronic disability in older adults (Gates and Mills, 2005). The impairments of peripheral (sensory or strial) and central (predominantly neural) auditory pathways, diagnosed with different procedures, are often variously imbricated in determining ARHI, with mixed clinical findings (Gates and Mills, 2005). A growing body of epidemiological evidence linking ARHI with late-life cognitive disorders (Panza et al., 2015a) suggested the potential for correcting hearing loss so that elders can function better also from a cognitive point of view with appropriate treatment. ARHI is also a substantial marker for frailty in older age, another age-related clinical condition for identifying older persons at elevated risk for numerous adverse health outcomes such as falls, institutionalization, hospitalization, disability, and death (Rodriguez-Manas, 2013). Frailty is as a multidimensional syndrome characterized by a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to stressors (Rodriguez-Manas, 2013). Although there is no consensus regarding the operational definition of frailty, in general, two are the most frequently used approaches: the first is the physical or “phenotypic” model of frailty, while the second is based on deficit accumulation, measured with the so called frailty indexes, and defined as an accumulation of health-related deficits and disorders (Rodriguez-Manas, 2013). However, also psychological, cognitive and social factors are part of this multidimensional syndrome, with great influence on its definition and treatment. Cognition has already been suggested as a possible component of frailty with increased risk of adverse outcomes. Therefore, the prevention of cognitive-related adverse outcomes including delirium (Eeles et al., 2012) and late-life cognitive disorders (Robertson et al., 2013; Panza et al., 2015b) may be possible also through frailty prevention.

Psychometric Properties of a Decisional Capacity Screening Tool for Individuals Contemplating Participation in Alzheimer's Disease Research.

With the growing population of individuals affected by Alzheimer's disease (AD) and related disorders, there is a pressing demand for research on late-life cognitive disorders. However, this population's high risk for decisional incapacity necessitates evaluation of capacity to consent to research participation, adding cost and complexity to the research process. The University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) was initially validated in a sample of persons with schizophrenia and healthy controls. To assess the psychometric properties of the UBACC when used in a sample of individuals contemplating participation in AD research. The UBACC was administered to a convenience sample (n = 132) consisting of individuals with mild to moderate cognitive impairment (n = 52), their study partners (n = 52), and healthy older adults control subjects (n = 30), as part of a broader study to evaluate perceived burden of research participation. Reliability tests, correlational analyses, and exploratory factor analytic methods were used to examine the psychometric properties of the instrument. UBACC scores were significantly associated with both global cognition (rs= 0.564, p < 0.001) and verbal fluency (rs = 0.511, p < 0.001), indicating concurrent validity with related constructs. The resulting factor structure differed from that reported by the developers in their initial testing. Items clustered almost entirely on one factor; items reflecting the construct of understanding accounted for 32.12% of total variance, with no evidence for distinct reasoning or appreciation scales. The UBACC shows promise when used to screen for decisional capacity among those considering participation in AD research.

Research Update: Healthy Aging and Prevention of Late-Life Mood and Cognitive Disorders (Sponsored by the AAGP Research Committee; Chaired by Helen Lavretsky, M.D.)

Research Update: Healthy Aging and Prevention of Late-Life Mood and Cognitive Disorders (Sponsored by the AAGP Research Committee; Chaired by Helen Lavretsky, M.D.)

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

Nutrition, frailty, and Alzheimer's disease.

Currently, available drugs for the treatment of Alzheimer's disease (AD) have only symptomatic effects, and there is an unmet need of preventing AD onset and delaying or slowing disease progression in absence of disease-modifying therapies. Substantial epidemiological evidence suggested the hypothesis that modifiable metabolic, vascular, and lifestyle-related factors may be linked to the development of late-life cognitive disorders (Solfrizzi et al., 2011). Among these proposed factors, one appealing link is the association between dietary habits and the occurrence of AD (Tangney, 2014). Among age-related conditions closely associated to dementia and cognitive disorders in late life, frailty is a multidimensional geriatric condition that reflects a multisystem physiological change and a nonspecific state of vulnerability (Fried et al., 2001), with an increased risk for different adverse health outcomes in older age, including disability, falls, hospitalizations, and all-cause mortality (Fried et al., 2001). Although the operational definition of frailty is still controversial, in general, two approaches predominate. The “phenotypic” or physical definition of frailty or the “biological syndrome model” proposed five components: exhaustion, unintentional weight loss, weakness, slow walking speed, and low levels of physical activity. The frail state is defined by the presence of three or more of these components, the pre-frail state is defined by only one or two of these characteristics, while older individuals are “robust” when they have none of these frailty components (Fried et al., 2001). Other definitions, criticizing this concept, promote a multidimensional approach with a definition of frailty based on a cumulative model, employing frailty indexes for the evaluation of this condition, calculated by considering the accumulation of potential deficits, i.e., the presence of diseases, abnormal laboratory values, symptoms, signs, or disabilities (Rockwood et al., 2004). For all frailty models, cognitive and affective disorders, physical activity, and nutritional status have been suggested as markers of frailty (Kelaiditi et al., 2014). In particular, cognition has been considered a major component of frailty, also associated with adverse health outcomes (Rockwood et al., 2004). Therefore, possible preventive interventions on cognitive-related outcomes of frailty, including AD and dementia, may be operated though the prevention of this geriatric syndrome and its associated components (Panza et al., 2011; Robertson et al., 2013). Of note, in frailty prevention, the impaired nutrition, and weight loss of frail older subjects may be addressed by focused nutritional interventions.

Natural products and supplements for geriatric depression and cognitive disorders: an evaluation of the research.

Numerous geriatric patients are using Complementary and Alternative Medicine (CAM) for late-life mood and cognitive disorders. Natural products and supplements are a common CAM intervention which have risks and benefits of which patients should be appropriately advised. The data for omega-3 fatty acids, ginkgo biloba, SAMe, St John's wort, B vitamins and vitamin D, huperzine, caprylidene, and coconut oil will be evaluated. Since the evidence basis for natural products and supplements is limited, especially for the geriatric population, studies involving the general adult population are included to infer effects in the aging population. Despite the data available, more rigorous studies with larger sample sizes over longer periods of time are still needed. Regardless of a physician's preference to recommend various natural supplements and products, a physician could protect their patients by having an understanding of the side effects and indications for various natural products.