A Possible Reversible Cause of Cognitive Impairment: Undiagnosed Cirrhosis and Potential Hepatic Encephalopathy in Patients with Dementia.

BACKGROUND: Dementia and hepatic encephalopathy (HE) have symptom overlap and are challenging to differentiate. The presence of undiagnosed cirrhosis may lead to missed opportunities to treat HE, which was found in a Veterans database. This needs validation in a non-Veteran cohort. METHODS: A retrospective cohort study was conducted between 2009 and 2019 using national non-Veteran patient data from the multi-center TriNetX database. Participants included 68,807 patients with a dementia diagnosis at ≥2 visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) index, which indicates liver disease. Prevalences of high FIB-4 scores (>2.67 and >3.25) were measured within the cohort, and associations between high FIB-4 and comorbidities/demographics were examined. RESULTS: Within the cohort (44.7% male, 78.0% white, mean age 72.73 years (±11.09)), 7.6% (n = 5815) had a FIB-4 index >3.25 and 12.8% (n=8683) had FIB-4 >2.67. In multivariable logistic regression models, FIB-4 > 3.25 was associated with male gender (OR: 1.42 [1.33-1.51]), congestive heart failure (OR:1.73 [1.59-1.87]), viral hepatitis (OR: 2.23 [1.84-2.68]), alcohol use disorder (OR: 1.39 [1.22-1.58]), and chronic kidney disease (OR: 1.38 [1.28-1.48]), and inversely associated with white race (OR: 0.76 [0.71-0.82]) and diabetes (OR: 0.82 [0.77-0.88]). Similar findings were associated with the FIB-4 > 2.67 threshold. CONCLUSION: The findings of this national cohort suggest that the FIB-4 index could be utilized to screen for potential undiagnosed cirrhosis in patients with dementia and that hepatic encephalopathy that might be misdiagnosed as dementia or cause worsening of cognitive function in patients with dementia.

Undiagnosed Cirrhosis and Hepatic Encephalopathy in a National Cohort of Veterans With Dementia.

Importance: Dementia and hepatic encephalopathy (HE) are challenging to distinguish clinically. Undiagnosed cirrhosis in a patient with dementia can lead to missed opportunities to treat HE. Objective: To examine the prevalence and risk factors of undiagnosed cirrhosis and therefore possible HE in veterans with dementia. Design, Setting, and Participants: A retrospective cohort study was conducted between 2009 and 2019 using data from the Veterans Health Administration (VHA) and 2 separate validation cohorts from the Richmond Veterans Affairs Medical Center. Data analysis was conducted from May 20 to October 15, 2023. Participants included 177 422 US veterans with a diagnosis of dementia at 2 or more clinic visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) score. Exposures: Demographic and clinical characteristics. Main Outcomes and Measures: An FIB-4 score (>2.67 suggestive of advanced fibrosis and >3.25 suggestive of cirrhosis), capped at age 65 years even for those above this cutoff who were included in the analysis. Results: Among 177 422 veterans (97.1% men; 80.7% White; mean (SD) age, 78.35 [10.97] years) 5.3% (n = 9373) had an FIB-4 score greater than 3.25 and 10.3% (n = 18 390) had an FIB-4 score greater than 2.67. In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with older age (odds ratio [OR], 1.07; 95% CI, 1.06-1.09), male gender (OR, 1.43; 95% CI, 1.26-1.61), congestive heart failure (OR, 1.48; 95% CI, 1.43-1.54), viral hepatitis (OR, 1.79; 95% CI, 1.66-1.91), Alcohol Use Disorders Identification Test score (OR, 1.56; 95% CI, 1.44-1.68), and chronic kidney disease (OR, 1.11; 95% CI, 1.04-1.17), and inversely associated with White race (OR, 0.79; 95% CI, 0.73-0.85), diabetes (OR, 0.78; 95% CI, 0.73-0.84), hyperlipidemia (OR, 0.84; 95% CI, 0.79-0.89), stroke (OR, 0.85; 95% CI, 0.79-0.91), tobacco use disorder (OR, 0.78; 95% CI, 0.70-0.87), and rural residence (OR, 0.92; 95% CI, 0.87-0.97). Similar findings were associated with the FIB-4 greater than 2.67 threshold. These codes were associated with cirrhosis on local validation. A local validation cohort of patients with dementia showed a similar percentage of high FIB-4 scores (4.4%-11.2%). Conclusions and Relevance: The findings of this cohort study suggest that clinicians encountering patients with dementia should be encouraged to screen for cirrhosis using the FIB-4 score to uncover reversible factors associated with cognitive impairment, such as HE, to enhance outcomes.

Specific Challenges in Geriatric Cirrhosis and Hepatic Encephalopathy.

As the world's population ages, diseases predominantly found in the elderly now overlap with diseases that were thought to be the purview of younger patients. This includes chronic liver disease, which affects more than 2 billion people worldwide. Owing to the obesity epidemic (and associated metabolic diseases), nonalcoholic fatty liver disease has become the most common cause of chronic liver disease and cirrhosis. A major complication of cirrhosis is hepatic encephalopathy (HE), which becomes challenging to diagnose in elderly patients. HE is usually included in the differential diagnosis of acute delirium but not of reversible dementias. To illustrate this point, we present 2 cases of older patients that were misdiagnosed as having dementia and Parkinson's disease or a parkinsonian syndrome but had contributions from cirrhosis. Both cognitive impairment and tremor resolved with treatment of HE.

Caring for older veterans with chronic low back pain using a geriatric syndrome approach: Rationale and methods for the aging back clinics (ABC) trial.

The purpose of the ongoing trial is to improve care of older Veterans with chronic low back pain (CLBP, i.e., low back pain for ≥6 months on ≥ half the days). Current CLBP care is limited by being either overly spine-focused or non-specifically prescribed and both approaches frequently lead to suboptimal reduction in pain and improvement in function. Through prior studies we have laid the foundation for a patient-centered approach to care for older Veterans with CLBP in which the spine is a source of vulnerability but not the sole treatment target. The approach considers CLBP a geriatric syndrome, a final common pathway for the expression of multiple contributors rather than a disease of the spine. We describe here the rationale and design of a randomized controlled trial to test the efficacy of an older Veteran-centered approach to CLBP care in "Aging Back Clinics (ABCs)" compared with Usual Care (UC). Three hundred thirty Veterans age 65-89 with CLBP will be randomized to ABCs or UC and followed for 12 months after randomization. We will assess the impact of ABCs on our primary outcome of pain-associated disability with the Oswestry Disability Index at 6 and 12 months, and secondary outcomes of pain intensity, health-related quality of life, balance confidence, mobility and healthcare utilization. If shown efficacious, the approach tested in ABCs has the potential to transform the care of older adults with CLBP by improving the quality of life for millions, reducing morbidity and saving substantial healthcare costs.

Aging Back Clinics-a Geriatric Syndrome Approach to Treating Chronic Low Back Pain in Older Adults: Results of a Preliminary Randomized Controlled Trial.

OBJECTIVE: Treating chronic low back pain (CLBP) with spine-focused interventions is common, potentially dangerous, and often ineffective. This preliminary trial tests the feasibility and efficacy of caring for CLBP in older adults as a geriatric syndrome in Aging Back Clinics (ABC). DESIGN: Randomized controlled trial. SETTING: Outpatient clinics of two VA Medical Centers. SUBJECTS: Fifty-five English-speaking veterans aged 60-89 with CLBP and no red flags for serious underlying illness, prior back surgery, dementia, impaired communication, or uncontrolled psychiatric illness. METHODS: Participants were randomized to ABC care or usual care (UC) and followed for six months. ABC care included 1) a structured history and physical examination to identify pain contributors, 2) structured participant education, 3) collaborative decision-making, and 4) care guided by condition-specific algorithms. Primary outcomes were low back pain severity (0-10 current and seven-day average/worst pain) and pain-related disability (Roland Morris). Secondary outcomes included the SF-12 and health care utilization. RESULTS: ABC participants experienced significantly greater reduction in seven-day average (-1.22 points, P = 0.023) and worst pain (-1.70 points, P = 0.003) and SF-12 interference with social activities (50.0 vs 11.5%, P = 0.0030) at six months. ABC participants were less likely to take muscle relaxants (16.7 vs 42.3%, P = 0.0481). Descriptively, UC participants were more likely to experience pain-related emergency room visits (45.8% vs 30.8%) and to be exposed to non-COX2 nonsteroidal anti-inflammatory drugs (73.1% vs 54.2%). CONCLUSIONS: These preliminary data suggest that ABC care for older veterans with CLBP is feasible and may reduce pain and exposure to other potential morbidity.

Biopsychosocial Profiles and Functional Correlates in Older Adults with Chronic Low Back Pain: A Preliminary Study.

OBJECTIVE: To describe key peripheral and central nervous system (CNS) conditions in a group of older adults with chronic low back pain (CLBP) and their association with pain severity and self-reported and performance-based physical function. DESIGN: Cross-sectional. SETTING: Outpatient VA clinics. SUBJECTS: Forty-seven community-dwelling veterans with CLBP (age 68.0 ± 6.5 years, range = 60-88 years, 12.8% female, 66% white) participated. METHODS: Data were collected on peripheral pain generators-body mass index, American College of Rheumatology hip osteoarthritis criteria, neurogenic claudication (i.e., spinal stenosis), sacroiliac joint (SIJ) pain, myofascial pain, leg length discrepancy (LLD), and iliotibial band pain; and CNS pain generators-anxiety (GAD-7), depression (PHQ-9), insomnia (Insomnia Severity Index), maladaptive coping (Fear Avoidance Beliefs Questionnaire, Cognitive Strategies Questionnaire), and fibromyalgia (fibromyalgia survey). Outcomes were pain severity (0 to 10 scale, seven-day average and worst), self-reported pain interference (Roland Morris [RM] questionnaire), and gait speed. RESULTS: Approximately 96% had at least one peripheral CLBP contributor, 83% had at least one CNS contributor, and 80.9% had both peripheral and CNS contributors. Of the peripheral conditions, only SIJ pain and LLD were associated with outcomes. All of the CNS conditions and SIJ pain were related to RM score. Only depression/anxiety and LLD were associated with gait speed. CONCLUSIONS: In this sample of older veterans, CLBP was a multifaceted condition. Both CNS and peripheral conditions were associated with self-reported and performance-based function. Additional investigation is required to determine the impact of treating these conditions on patient outcomes and health care utilization.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part X: Sacroiliac Joint Syndrome.

OBJECTIVE: To present an algorithm of sequential treatment options for managing sacroiliac joint (SIJ) pain in the setting of chronic low back pain (CLBP) in the older adult. This is the tenth part in a series, and includes an illustrative clinical case. METHODS: The stepped care drug table and evaluation and treatment algorithm were created following a thorough literature review of approaches and subsequent analysis through a modified Delphi process. The principal investigator developed the initial draft, which was refined for content by an interdisciplinary panel of five experts. The refined materials were then assessed for the feasibility of implementation and validity of recommendations for older adults in a primary care setting by a panel of nine primary care providers. While not exclusive to Veteran's Health Administration (VHA) facilities, an emphasis was made to include resources and medications available to providers in the VHA. RESULTS: The algorithm and drug table developed to systematically identify and address SIJ pain in the older adult is presented here. The process should begin with recognizing the presenting symptoms of CLBP stemming from the SI region, and supporting physical exam testing using the compression test and thigh thrust maneuver. Identification of the SIJ as a pain generator is followed by assessment and treatment of contributory factors. SIJ pain treatment should begin with education and self-management including exercise, and may escalate to include interventional procedures and/or referral to a pain rehabilitation program. CONCLUSIONS: Pain originating from the SIJ is often under-recognized, but a structured and consistent approach can help identify older patients who would benefit from treatment of this contributor to CLBP. KEY WORDS: Chronic Low Back Pain; Sacroiliac Joint Pain; Older Adults.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part VII: Insomnia.

OBJECTIVE : To present the seventh in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on insomnia and presents a treatment algorithm for managing insomnia in older adults, along with a representative clinical case. METHODS : A modified Delphi process was used to develop the algorithm and supportive materials. A multidisciplinary expert panel representing expertise in health psychology and sleep medicine developed the algorithm and supporting documents that were subsequently refined through an iterative process of input from a primary care provider panel. RESULTS : We present an illustrative clinical case and an algorithm to help guide the care of older adults with insomnia, an important contributor to CLBP and disability. Multicomponent cognitive behavioral therapy for insomnia (CBTI) and similar treatments (e.g., brief behavioral treatment for insomnia [BBTI]) are the recommended first-line treatment. Medications should be considered only if BBTI/CBTI is suboptimal or not effective and should be prescribed at the lowest effective dose for short periods of time (< 90 days). CONCLUSIONS : Insomnia is commonly comorbid with CLBP in older adults and should be routinely evaluated and treated because it is an important contributor to pain and disability. The algorithm presented was structured to assist primary care providers in planning treatment for older adults with CLBP and insomnia.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VI: Lumbar Spinal Stenosis.

OBJECTIVE: . To present the sixth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on the evaluation and management of lumbar spinal stenosis (LSS), the most common condition for which older adults undergo spinal surgery. METHODS: . The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The illustrative clinical case was taken from the clinical practice of a contributor's colleague (SR). RESULTS: . We present an algorithm and supportive materials to help guide the care of older adults with LSS, a condition that occurs not uncommonly in those with CLBP. The case illustrates the importance of function-focused management and a rational approach to conservative care. CONCLUSIONS: . Lumbar spinal stenosis exists not uncommonly in older adults with CLBP and management often can be accomplished without surgery. Treatment should address all conditions in addition to LSS contributing to pain and disability.

Deconstructing Chronic Low Back Pain in the Older Adult--Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part V: Maladaptive Coping.

OBJECTIVE: As part of a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults, this article focuses on maladaptive coping--a significant contributor of psychological distress, increased pain, and heightened disability in older adults with CLBP. METHODS: A modified Delphi technique was used to develop a maladaptive coping algorithm and table providing the rationale for the various components of the algorithm. A seven-member content expert panel and a nine-member primary care panel were involved in the iterative development of the materials. While the algorithm was developed keeping in mind resources available within the Veterans Health Administration (VHA) facilities, panelists were not exclusive to the VHA, and therefore, materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributors' clinical practice. RESULTS: We present a treatment algorithm and supporting table to be used by providers treating older adults who have CLBP and engage in maladaptive coping strategies. A case of an older adult with CLBP and maladaptive coping is provided to illustrate the approach to management. CONCLUSIONS: To promote early engagement in skill-focused treatments, providers can routinely evaluate pain coping strategies in older adults with CLBP using a treatment algorithm.

Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IV: Depression.

OBJECTIVE: To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression. METHODS: The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a three-member content expert panel, and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. RESULTS: We present an algorithm and supportive materials to help guide the care of older adults with depression, an important contributor to CLBP. The case illustrates an example of a complex clinical presentation in which depression was an important contributor to symptoms and disability in an older adult with CLBP. CONCLUSIONS: Depression is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatments can be planned and implemented.

Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome.

OBJECTIVE: To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS: A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS: Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS: Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability.

Deconstructing chronic low back pain in the older adult--step by step evidence and expert-based recommendations for evaluation and treatment: part I: Hip osteoarthritis.

OBJECTIVE: To present the first in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on hip osteoarthritis (OA). METHODS: The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. RESULTS: We present an algorithm and supportive materials to help guide the care of older adults with hip OA, an important contributor to CLBP. The case illustrates an example of complex hip-spine syndrome, in which hip OA was an important contributor to disability in an older adult with CLBP. CONCLUSIONS: Hip OA is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatment can be designed.

The importance of "high valence" events in a successful program for teaching geriatrics to medical students.

Virginia Commonwealth University developed an enhanced medical student geriatric curriculum that includes required home visits and nursing home visits for second year students (180 per year), an annual Forum on Aging for all first and second year students, and small group exercises. We added 30 hours of basic science material to pre-clinical courses and increased clinical exposure to geriatricians in third and fourth years. Student satisfaction with individual experiences was high. Persistent effects of "high valence" required activities, where emotion played a role, was shown by post-pre survey techniques and focus groups. Fourth year AAMC exit questionnaire items in areas addressed by this curriculum improved markedly between 2002 and 2006, while an internal control changed much less.

Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men.

We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after a baseline (B) study in randomized order with an intervening 3-month washout: transdermal T patch (5.0 mg/daily); recombinant human GH (6.25 micro g/kg sc daily); and combined hormones (GHT). ANOVA with repeated measures was used to evaluate interventional effects. Integrated serum GH concentrations [mean (SEM)] were elevated comparably by GH and GHT: [B = 363 (55), GH = 1107 (120), T = 459 (131), and GHT = 1189 (46) micro g/liter.min; P < 0.0001]. Serum IGF-I concentrations also increased commensurately after GH and GHT: [B = 168 (14), GH = 285 (16), T = 192 (25), and GHT = 294 (25) micro g/liter; P < 0.0001]. GHT administration increased total estradiol: [B = 110 (20), GH = 106 (13), T = 129 (13), and GHT = 153 (17) pmol/liter; P < 0.02], and both T and GHT elevated free T: [B = 12 (2.1), GH = 11 (1.5), T = 22 (2.8), and GHT = 24 (2.5) pg/ml; P < 0.0001]. No significant changes occurred in strength, flexibility, percentage body fat, or sexual function and mood. However, fat-free mass increased under combined GHT exposure: [B = 55 (1.3), GH = 56 (1.1), T = 55 (1.5), GHT = 57 (1.7) kg; P < 0.03]. Balance improved in response to GH intervention (P < 0.05), as did 30-m walk time during T and GHT interventions [B = 6.6 (0.3), GH = 6.2 (0.7), T = 5.9 (0.3), GHT = 5.5 (0.3) sec; P = 0.04] and stair climb time for all three interventions [B = 32.2 (1.4), GH = 29.8 (1.2), T = 30.5 (1.4), and GHT = 29.9 (1.2) sec (P = 0.0034), wherein the effects of GH, T, and GHT were different from that of B]. Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration (P < 0.05, compared with B). Myostatin and androgen receptor gene expression were not affected. Serum osteocalcin increased in response to the GH and GHT interventions: [B = 4.8 (0.52), GH = 5.7 (0.54), T = 4.7 (0.33), and GHT = 5.5 (0.39); P <0.009]. There were no significant adverse events during 30 patient-months of intervention. We conclude that 1 month of GH and/or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression.