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PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.
Gawlik-Kotelnicka, O, Margulska, A, Skowrońska, A, Strzelecki, D
Nutrients. 2023;15(6)
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Depression often coexists with metabolic abnormalities, and metabolic syndrome (MetS) is diagnosed in 30% of depressed subjects. Importantly, both obesity and MetS have been found to be independently associated with depressive symptoms and inflammation. The aim of this study was to investigate the effect of probiotics in the treatment of depressive disorders with possible comorbid MetS and its components. This study was an internal feasibility study based on the main randomised study - a single-centre, parallel-group, prospective, randomised, double-blind, placebo-controlled pilot trial. Adult patients (≥18 years) with depressive disorders were randomly assigned (1:1) into either the placebo or probiotic group. Results showed a positive association between probiotics supplementation and psychometric parameters together with the metabolic profile, serum inflammation markers, and biomarkers of metabolic-associated fatty liver disease in patients with depressive disorders. Authors conclude that the findings of their study would be suitable for determining the potential clinical use of probiotics and assessing certain key factors such as potential biomarkers of response.
Abstract
There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.
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Metabolic impact of a nutrition education program for the promotion of fruit and vegetable consumption with people with severe mental disorders (DIETMENT).
Foguet-Boreu, Q, Vilamala-Orra, M, Vaqué-Crusellas, C, Roura-Poch, P, Assens Tauste, M, Bori Vila, J, Santos-López, JM, Del Río Sáez, R
BMC research notes. 2022;15(1):122
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In patients with severe mental disorders, motivation to follow a healthy diet and lifestyle might be low. A diet rich in fruits and vegetables may improve metabolic syndrome, cardiovascular health and mental health. This randomised community-based clinical trial included seventy-four patients with severe mental disorders out of which 37.8% of the participants had schizophrenia or related disorders, 29.7% had bipolar disorder, 25.7% had depressive disorder, 4.1% had a personality disorder, and 2.7% had obsessive-compulsive disorder. The intervention group followed a four-week food education programme (DIETMENT) aimed at promoting fruit and vegetable consumption. A five-month post-intervention analysis showed no increase in participants diagnosed with metabolic syndrome in the intervention group, but an increase in participants diagnosed with metabolic syndrome in the control group. There was a significant reduction in the glomerular filtrate rate in the intervention group. In patients with severe mental disorders, more studies should be conducted to examine the health-promoting effects of adding more fruits and vegetables to the diet. Health professionals can use the results of this study to understand how fruits and vegetables contribute to reducing metabolic syndrome and heart disease risk.
Abstract
OBJECTIVES The aim of this study is to determine the metabolic impact of a nutrition education program on metabolic parameters and the presence of metabolic syndrome (MetS). RESULTS Seventy-four patients were included (mean age, 48.7 years [Standard deviation, SD: 10.8], 55.4% men). The diagnoses of SMD were 37.8% schizophrenia and related disorders; 29.7% bipolar disorder; 25.7% depressive disorder; 4.1% personality disorders; and 2.7% obsessive compulsive disorders. Thirty-seven individuals were distributed in both the intervention group (IG) and the control group (CG). In the IG the presence of MetS was 56.3% and in the CG 46.7%, with no statistically significant difference (p = 0.309). At the end of the study, glomerular filtrate decreased in the IG, body mass index and abdominal perimeter increased in both groups, and there were no changes in metabolic parameters between the groups. Between the baseline and the end of the study, there was no increase in the number of patients diagnosed with MetS (14 at both points); and in the CG the increase was from 8 to 12 (p = 0.005). An intervention based on fruit and vegetable intake could prevent progression to MetS in individuals with SMD, decreasing the likelihood of cardiovascular disease. Trial registration The trial was retrospectively registered on International Standard Randomised Controlled Trial Number (ISRCTN) Register on 11 March 2022 (ISRCTN12024347).
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A Randomized Controlled Trial of Fasting and Lifestyle Modification in Patients with Metabolic Syndrome: Effects on Patient-Reported Outcomes.
Jeitler, M, Lauche, R, Hohmann, C, Choi, KA, Schneider, N, Steckhan, N, Rathjens, F, Anheyer, D, Paul, A, von Scheidt, C, et al
Nutrients. 2022;14(17)
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The metabolic syndrome (MetS) is a condition characterized by the presence of at least three cardiovascular risk factors, such as abdominal obesity, hypertension, insulin resistance, and dyslipidaemia. The aim of this study was to assess effects of fasting followed by the Mind-Body Medicine in Integrative and Complementary Medicine (MICOM) lifestyle modification intervention in patients with MetS on patient-reported outcomes, compared to a lifestyle modification intervention only. This study is a single-blind, bicentre, randomized controlled study. Patients (n=145) were randomly assigned in a 1:1 ratio into one of the 2 groups: fasting and lifestyle modification or the lifestyle modification. They started with 2 vegan days (max. 1200 kcal/day), followed by 5 days of fasting (max. 350 kcal/day), and a stepwise reintroduction of food. Then they participated in the 10-week MICOM comprehensive multimodal lifestyle modification intervention with weekly 6-h sessions. Results show that after the multimodal lifestyle modification intervention, there were improvements for all outcome measures, namely quality of life, anxiety, depression, stress, mood as well as self-efficacy, mindfulness, and self-compassion, which persisted at the follow-up after 24 weeks. Authors conclude that their findings show beneficial and clinically relevant effects of fasting and intensified lifestyle modification on quality of life and psychological parameters.
Expert Review
Conflicts of interest:
None
Take Home Message:
For clients with Metabolic syndrome a 5-day fast consisting of max. 350 kcal/day, in conjunction with therapies that focus on improved emotional, mental, social, spiritual, and behavioural factors may directly affect health and support improved mood.
Therapies include mindfulness and specific group training rooted in psycho-neuroendocrinology, and the use of formal meditation and gentle yoga exercises. As well as nutritional education included lectures, cooking workshops, as well as group support.
Bottom line: The use of complimentary therapies such as mindfulness, yoga and medication in conjunction with nutritional advice and may be effective to support improved mood in clients with Metabolic syndrome.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Metabolic syndrome (MetS) is a condition characterised by the presence of at least three cardiovascular risk factors such as abdominal obesity, hypertension, insulin resistance, and dyslipidemia.
The authors refer to epidemiological studies that have identified the role of psychological risk factors such as psychosocial stress, depression and anxiety in patients with MetS and cardiovascular disease.
This single-blind, bi-centre RCT assessed the effects of fasting followed by a comprehensive lifestyle modification program MICOM (Mind-Body Medicine in Integrative and Complementary Medicine) in 145 participants with Metabolic Syndrome (MetS) (62.8% women; 59.7 ± 9.3 years) randomised to:
1. 5-day fasting followed by 10 weeks of lifestyle modification (F + LM; modified DASH diet, exercise, mindfulness; n = 73) or
2. 10 weeks of lifestyle modification only (LM; n = 72)
The study duration was 24 weeks occurring from April 2014 to December 2014, with the last follow-up assessment in December 2015. 73 Participants were randomised into an F + LM group and 72 participants into an LM group between the ages of 59 and 60.
Outcomes were assessed at weeks 0, 1, 12, and 24, for quality of life (Short-Form 36 Health Survey Questionnaire, SF-36), anxiety/depression (Hospital Anxiety and Depression Scale, HADS), stress (Cohen Perceived Stress Scale, CPSS), mood (Profile of Mood States, POMS), self-efficacy (General Self-Efficacy Scale, GSE), mindfulness (Mindfulness Attention Awareness Scale, MAAS), and self-compassion (Self-Compassion Scale, SCS).
At week 1, POMS depression and fatigue scores were significantly lower in F + LM compared to LM. At week 12, most self-report outcomes improved in both groups—only POMS vigour was significantly higher in F + LM than in LM. Most of the beneficial effects within the groups persisted at week 24.
Clinical practice applications:
This randomised controlled trial highlights fasting-induced mood-modulating effects in the short term (<24 months).
LM induced several positive effects on quality of life and psychological parameters in participants with MetS.
The compliance rate for this study was good and there were no adverse effects reported suggesting a potentially effective lifestyle modification intervention for adults with metabolic syndrome.
The authors did note the extent to which participants adhered to the program by using stress reduction techniques at home was not assessed.
Considerations for future research:
MBM lifestyle modification intervention led to an improvement of self-efficacy, mindfulness, and self-compassion.
Further studies to explore explanatory models for the effects of MBM are needed.
Mediating variables on mindfulness, self-efficacy, and compassion, and the effects on physical and psychological parameters, need to be examined more closely.
Future studies could use condition-specific questionnaires in addition to generic ones, which have previously been used to facilitate the comparison of the study results with those in the population.
Abstract
Lifestyle interventions can have a positive impact on quality of life and psychological parameters in patients with metabolic syndrome (MetS). In this randomized controlled trial, 145 participants with MetS (62.8% women; 59.7 ± 9.3 years) were randomized to (1) 5-day fasting followed by 10 weeks of lifestyle modification (F + LM; modified DASH diet, exercise, mindfulness; n = 73) or (2) 10 weeks of lifestyle modification only (LM; n = 72). Outcomes were assessed at weeks 0, 1, 12, and 24, and included quality of life (Short-Form 36 Health Survey Questionnaire, SF-36), anxiety/depression (Hospital Anxiety and Depression Scale, HADS), stress (Cohen Perceived Stress Scale, CPSS), mood (Profile of Mood States, POMS), self-efficacy (General Self-Efficacy Scale, GSE), mindfulness (Mindfulness Attention Awareness Scale, MAAS), and self-compassion (Self-Compassion Scale, SCS). At week 1, POMS depression and fatigue scores were significantly lower in F + LM compared to LM. At week 12, most self-report outcomes improved in both groups-only POMS vigor was significantly higher in F + LM than in LM. Most of the beneficial effects within the groups persisted at week 24. Fasting can induce mood-modulating effects in the short term. LM induced several positive effects on quality of life and psychological parameters in patients with MetS.
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Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition.
Sala-Vila, A, Fleming, J, Kris-Etherton, P, Ros, E
Advances in nutrition (Bethesda, Md.). 2022;13(5):1584-1602
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α-Linolenic acid (ALA) is an omega-3 fatty acid found in seeds and nuts such as flaxseeds, chia seeds, and walnuts and in oils such as canola oil, soybean oil, flaxseed oil and walnut oil. It has been shown to reduce the risk of coronary heart disease and cardiovascular disease. This meta-analysis examined the results of various studies, including epidemiologic studies, randomized controlled trials, and systematic reviews, to evaluate the beneficial effects of ALA in improving cognitive function and reducing the risk of cardiovascular disease and coronary heart disease. The included studies showed a correlation between ALA intake and a decreased risk of cardiovascular disease and coronary heart disease, possibly due to ALA's anti-inflammatory properties, as well as its ability to reduce total cholesterol, LDL cholesterol, triglycerides, and blood pressure. The analysis also found that ALA intake may reduce the risk of type 2 diabetes and cognitive impairment. Healthcare professionals can leverage the findings of this analysis to educate individuals about the benefits of dietary ALA in improving cardiovascular and cognitive outcomes. However, further studies are necessary to establish definitive conclusions and determine therapeutic dosage.
Abstract
Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.
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Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.
Fitzgerald, KC, Vizthum, D, Henry-Barron, B, Schweitzer, A, Cassard, SD, Kossoff, E, Hartman, AL, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
Multiple sclerosis and related disorders. 2018;23:33-39
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Multiple sclerosis (MS) is a disease of the central nervous system. Dietary modification is emerging as a safe intervention to potentially modify disease course. The main aim of this study was to assess the safety and feasibility of an intermittent fasting diet in people with MS. Secondary outcomes explored the effects of calorie restriction (CR) diets on body weight and anthropometric characteristics as well as on patient-reported outcomes including fatigue, sleep and mood. The study is a pilot randomised controlled feeding study of three different types of diets. Each participant (n=36) was randomized to 1 of 3 diets: a control diet (placebo), a daily CR diet and intermittent CR diet. Results indicate that daily CR diet was associated with marginally greater weight loss than the intermittent CR diet. Both CR diets were associated with trends toward improvements in cardiometabolic outcomes. Furthermore, CR diets were associated with in improvements in emotional well-being. Authors conclude that CR and weight loss represent interventions for clinically relevant symptoms due to MS, such as emotional well-being, without adding meaningful risks or adverse outcomes.
Abstract
An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.
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Prevalence and determinants of physical activity in a mixed sample of psychiatric patients in Saudi Arabia.
Alosaimi, FD, Abalhasan, MF, Alhabbad, AA, Fallata, EO, Haddad, BA, AlQattan, NI, Alassiry, MZ
Saudi medical journal. 2018;39(4):401-411
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Physical activity has been shown to considerably reduce the burden of several non-communicable disorders (are diseases of long duration and generally slow progression), such as heart disease, stroke, diabetes, and breast and colon cancers. The aim of the study is to estimate the prevalence of physical activity among a mixed group of patients with psychiatric illnesses in Saudi Arabia. Furthermore, the study sought to evaluate the associations between physical activity, patients with different psychiatric diagnoses and the use of psychotropic medications. The study is a cross-sectional observational study that recruited 1185 patients seeking psychiatric advice, with an average age of 38.0±13.0 years. Results indicate a low prevalence of physical activity in a large, mixed sample of patients with psychiatric illnesses in both inpatient and outpatient settings in Saudi Arabia. Authors conclude that physical activity levels vary according to the type of psychiatric disease and the medications used. They outline that it is important to assess the physical activity status in patients with psychiatric illnesses and promote physical activity programs among psychiatric patients.
Abstract
OBJECTIVES To estimate prevalence of physical activity and its associations with various psychiatric disorders and the use of psychotropic medications. METHODS A cross-sectional observational study was carried out between July 2012 and June 2014. Patients were enrolled from a number of hospitals located in 5 regions of the Kingdom of Saudi Arabia. RESULTS A total of 1185 patients were included in current analysis: 796 were outpatients, and 389 were inpatients. Out of 1,185 patients, 153 (12.9%) were physically active. Much higher rates of physical activity were reported among males than females (15.9% versus 9.6%, p less than 0.001). According to the univariate analysis, higher rates of physical activity were positively correlated with primary bipolar disorders, the use of antianxiety medications and, to a lesser extent, use of antipsychotic medications, but they were negatively correlated with primary anxiety disorders, use of antidepressant medications, and use of multiple psychotropic medications. The associations between physical activity and primary bipolar disorders (odds ratio [OR]=2.47, p=0.002), use of antianxiety medications (OR=3.58, p=0.003), and use of multiple psychotropic medications (OR=0.33, p less than 0.001) remained significant after adjusting for demographic and clinical characteristics. CONCLUSION We report a variable but generally low prevalence of physical activity among a large, mixed sample of psychiatric patients in Saudi Arabia. These findings may highlight the importance of assessing physical activity status of psychiatric patients and the critical need for physical activity promotion programs among this group of disadvantaged patients.
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Association between weight bias internalization and metabolic syndrome among treatment-seeking individuals with obesity.
Pearl, RL, Wadden, TA, Hopkins, CM, Shaw, JA, Hayes, MR, Bakizada, ZM, Alfaris, N, Chao, AM, Pinkasavage, E, Berkowitz, RI, et al
Obesity (Silver Spring, Md.). 2017;25(2):317-322
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Weight stigma is a psychosocial consequence in which individuals with obesity experience public discrimination and devaluation. Some individuals apply these negative stereotypes to themselves, which creates a self-directed stigma referred to as weight bias internalization (WBI). While studies have found perceived weight discrimination to be associated with an increased risk of mortality, no study has investigated the relationship between WBI and obesity on the risk of developing metabolic syndrome (MetS). The aim of this study is to examine the relationship between WBI and MetS. The authors hypothesised that among obese individuals, higher levels of WBI would be associated with increased odds of having MetS. Among the 178 obese adults recruited, 159 completed the study. Tests included anthropometric measurements, blood analysis, the Weight Bias Internalization Scale (WBIS) and the Patient Health Questionnaire. This study found that individuals who self-stigmatise may have a heightened risk of dyslipidemia, one component of MetS. Based on these results, the authors conclude that weight stigma is a chronic stressor and may contribute to poor health. Future studies are needed to identify specific pathways in which WBI exacerbates cardiometaoblic risk factors.
Abstract
OBJECTIVE Weight stigma is a chronic stressor that may increase cardiometabolic risk. Some individuals with obesity self-stigmatize (i.e., weight bias internalization, WBI). No study to date has examined whether WBI is associated with metabolic syndrome. METHODS Blood pressure, waist circumference, and fasting glucose, triglycerides, and high-density lipoprotein cholesterol were measured at baseline in 178 adults with obesity enrolled in a weight-loss trial. Medication use for hypertension, dyslipidemia, and prediabetes was included in criteria for metabolic syndrome. One hundred fifty-nine participants (88.1% female, 67.3% black, mean BMI = 41.1 kg/m2 ) completed the Weight Bias Internalization Scale and Patient Health Questionnaire (PHQ-9, to assess depressive symptoms). Odds ratios and partial correlations were calculated adjusting for demographics, BMI, and PHQ-9 scores. RESULTS Fifty-one participants (32.1%) met criteria for metabolic syndrome. Odds of meeting criteria for metabolic syndrome were greater among participants with higher WBI, but not when controlling for all covariates (OR = 1.46, 95% CI = 1.00-2.13, P = 0.052). Higher WBI predicted greater odds of having high triglycerides (OR = 1.88, 95% CI = 1.14-3.09, P = 0.043). Analyzed categorically, high (vs. low) WBI predicted greater odds of metabolic syndrome and high triglycerides (Ps < 0.05). CONCLUSIONS Individuals with obesity who self-stigmatize may have heightened cardiometabolic risk. Biological and behavioral pathways linking WBI and metabolic syndrome require further exploration.
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Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen, DE
Aging. 2016;8(2):304-13
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Alzheimer’s disease (AD) is the third leading cause of death in the USA, with around 5.2 million Americans diagnosed with AD. Effective treatment with medications has yet to be found. A recent multiple therapy programme (originally known as MEND, now called ReCODE) proposed by Professor Bredesen and team, has shown some promising anecdotal results. Identifying sub-types of AD has been proposed as a means to develop targeted protocols for treatment. Recently, 3 sub-types of AD have been described: Type 1 (inflammatory), Type 2 (non-inflammatory or decreasing brain size) and Type 3 (damage to the outer layer of the cerebrum). This report describes 7 patients with Type 3 AD. Type 3 AD is characterised by exposure to specific toxins (usually inhaled) and is often associated with Chronic Inflammatory Response Syndrome (CIRS). The report provides the symptoms, signs and laboratory values representative of Type 3 AD and could be used by Nutrition Practitioners to help with implementation of appropriate nutrition protocols when working with clients with AD.
Abstract
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave.