Primitive reflexes and dementia in older adults: a meta-analysis of observational and cohort studies.

Primitive reflexes (PRs) are clinical signs that indicate diffuse cerebral dysfunction and frontal lesions. We aimed to present a comprehensive analysis of the prevalence and risk of PRs in patients with dementia. English-language articles published from January 1990 to April 2021 were searched in PubMed, ScienceDirect, Cochrane, and Web of Science with keywords. The titles and abstracts of the identified articles were screened to identify potentially relevant papers. Odds ratios and risk ratios were extracted with 95% confidence intervals and combined using the random-effects model after logarithmic transformation. The prevalence in dementia patients was also combined using the random-effects model. This meta-analysis involved 29 studies. The snout reflex (48% of cases) was the most prevalent. It was found that the risk of PRs in individuals with dementia was significantly elevated, ranging from 13.94 to 16.38 times higher than in healthy controls. The grasp reflex exhibited the highest risk for dementia. This meta-analysis showed that the prevalence and the risk of PRs is high in older patients with dementia. Therefore, PRs, especially the grasp reflex, should be carefully assessed as a part of routine physical examination in the diagnostic process for dementia.

Impact of diabetes on weight loss outcomes after bariatric surgery: Experience from 5-year follow-up of Michigan Bariatric Surgery Cohort.

OBJECTIVE: For patients with obesity and diabetes, bariatric surgery can lead to the remission of both diseases. However, the possible impact of diabetes on the magnitude of weight loss outcomes after bariatric surgery has not been precisely quantified. RESEARCH DESIGN AND METHODS: Data from Michigan Bariatric Surgery Cohort (MI-BASiC) was extracted to examine the effect of baseline diabetes on weight loss outcomes. Consecutive patients older than 18 years of age undergoing gastric bypass (GB) or sleeve gastrectomy (SG) for obesity at University of Michigan between January 2008 and November 2013 were included. Repeated measures analysis was used to determine if diabetes was a predictor of weight loss outcomes over 5 years postsurgery. RESULTS: Out of the 714 included patients, 380 patients underwent GB [mean BMI 47.3 ± 0.4 kg/m2 , diabetes 149 (39.2%)] and 334 SG [mean BMI 49.9 ± 0.5 kg/m2 , diabetes 108 (32.3%)]. Multivariable repeated measures analysis showed, after adjusting for covariates, that individuals with diabetes had a significantly lower percentage of total (p = .0023) and excess weight loss (p = .0212) compared to individuals without diabetes. CONCLUSIONS: Our data demonstrate that patients with diabetes undergoing bariatric surgery would experience less weight loss than patients without diabetes.

Orthostatic hypotension in dementia with Lewy bodies: a meta-analysis of prospective studies.

PURPOSE: Orthostatic hypotension (OH), one of the supportive clinical features in the diagnosis of dementia with Lewy bodies (DLB), is a significant problem in advanced age because of its severe negative consequences. The aim of this meta-analysis was to investigate the prevalence and risk of OH in patients with DLB. METHODS: The indexes and databases cited to identify relevant studies were PubMed, ScienceDirect, Cochrane, and Web of Science. The keywords for the search were "Lewy body dementia" and "autonomic dysfunction" or "dysautonomia" or "postural hypotension" or "orthostatic hypotension." English-language articles published from January 1990 to April 2022 were searched. The Newcastle-Ottawa scale was applied to evaluate the quality of the studies. Odds ratios (OR) and risk ratios (RR) were extracted with 95% confidence intervals (CI) and combined using the random effects model after logarithmic transformation. The prevalence in the patients with DLB was also combined using the random effects model. RESULTS: Eighteen studies (10 case controls and 8 case series) were included to evaluate the prevalence of OH in patients with DLB. Higher rates of OH were found to be associated with DLB (OR 7.71, 95% CI 4.42, 13.44; p < 0.001), and 50.8% of 662 patients had OH. CONCLUSION: DLB increased the risk of OH by 3.62- to 7.71-fold compared to healthy controls. Therefore, it will be useful to evaluate postural blood pressure changes in the follow-up and treatment of patients with DLB.

Orthostatic hypotension in patients with Alzheimer's disease: a meta-analysis of prospective studies.

BACKGROUND: Orthostatic hypotension (OH) is a clinical sign associated with severe adverse health outcomes in older adults. It has been reported to be common in patients with Alzheimer's disease (AD). The present meta-analysis aimed to investigate the prevalence and risk of OH in AD patients. METHODS: English-language articles published from January 1990 to August 2020 were searched in PubMed, ScienceDirect, Cochrane, and Web of Science with the keywords "Alzheimer" and "autonomic dysfunction" or "dysautonomia" or "postural hypotension" or "orthostatic hypotension." All prospective clinical studies (case-control, cohort, and cross-sectional studies, and randomized controlled trials) that were regarded as pertinent were included in this study. For quality assessment, the Newcastle-Ottawa Scale was used. Odds ratios (OR) and risk ratios (RR) were extracted with 95% confidence intervals (CI) and combined using the random effects model after logarithmic transformation. The prevalence in the AD patients was also combined using the random effects model. RESULTS: The meta-analysis involved 11 studies (7 case-control and 4 case series) to assess the risk of OH in AD. It was found that AD increased the risk of OH with an RR of 1.98 (95% CI: 0.97-4.04) and an OR of 2.53 (95% CI:1.10-5.86) compared to healthy controls, and OH was present in 28% (95% CI: 0.17-0.40) of 500 AD patients. CONCLUSION: There is an elevated risk of OH in AD by nearly 2.5-fold. Therefore, the evaluation of postural blood pressure changes should definitely be among the follow-up and treatment goals of AD.

The relationship between osteoporosis and sarcopenia, according to EWGSOP-2 criteria, in outpatient elderly.

INTRODUCTION: Osteoporosis and sarcopenia are significant health problems that mainly affect older adults. This study aimed to investigate the relationship between sarcopenia and osteoporosis. MATERIALS AND METHODS: The study included 444 participants who had undergone a dual-energy X-ray absorptiometry scan, handgrip test, 4-m walking speed test, and bioimpedance analysis within the past year. Participants were classified into control, osteopenia, or osteoporosis groups according to the World Health Organization classification. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People-2 criteria. RESULTS: The mean age of the participants was 75.88 ± 7.20 years, and 80.9% were females. There were 144, 230, and 70 participants in the osteoporosis, osteopenia, and control groups, respectively. Probable sarcopenia was identified in 94 subjects, sarcopenia in 61, and severe sarcopenia in 72 participants. After adjusting for age, gender, and body mass index, probable sarcopenia and severe sarcopenia were associated with osteoporosis (p < 0.05). Low muscle strength, and low physical performance were associated with osteoporosis (p < 0.02). When osteoporosis was evaluated only according to the femoral neck T score, low muscle strength and low physical performance were found to be related not only to osteoporosis (p < 0.001), but also to osteopenia (p < 0.05). Additionally, probable sarcopenia was associated with femoral neck osteopenia (p < 0.01). CONCLUSIONS: In this study, probable sarcopenia and severe sarcopenia were associated with osteoporosis in older adults. Furthermore, we found that low muscle strength, or dynapenia, which is the determining criterion of sarcopenia, was related to femoral neck osteopenia and osteoporosis.

Postprandial hypotension is more common than orthostatic hypotension in older adults with dementia with lewy bodies: a cross-sectional study.

Cardiovascular autonomic dysfunction is one of the supportive clinical features in dementia with Lewy bodies (DLB). This study aimed to investigate the frequency of postural and postprandial hypotension in people with DLB. The study group comprised 125 patients with DLB (76 females; mean age 78.4 ± 7.1 years) and 122 controls (88 females; mean age 74.4 ± 6.9 years). Postprandial blood pressure changes were assessed by ambulatory 24-hour blood pressure monitorization. Postural blood pressure changes were assessed via the head-up tilt table test. The frequency of postprandial hypotension (PPH) and orthostatic hypotension (OH) was higher in patients with DLB compared to controls (89.4% vs 51.7%; p < 0.001, and 45.5% vs 27.9%; p = 0.004, respectively) whereas the frequency of supine hypertension (SH), and orthostatic hypertension (OHT) was similar. However, SH in non-hypertensive participants was higher in DLB patients than in controls (48.9%, 25.7%; p = 0.035). PPH and OH were independently associated with a diagnosis of DLB (odds ratio [OR]:10.26 confidence interval [CI]%95 3.02-34.82; p < 0.001, and OR:2.22 CI%95 1.2-4.12; p = 0.012, respectively) after adjustment for age, number of medications, use of anti-psychotics drugs, angiotensin receptor blockers, and beta blockers. In conclusion, the study demonstrated that PPH was the most common finding of cardiovascular autonomic dysfunction, followed by OH and SH in older patients with DLB. Given the potential complications of postural blood pressure changes and PPH in such patients, cardiovascular autonomic dysfunction should be evaluated in patients with DLB.

Validity and reliability of the Turkish version of the Australian National University-Alzheimer's Disease Risk Index (ANU-ADRI).

INTRODUCTION: There is still a requirement for concise, practical scales that can be readily incorporated into everyday schedules and predict the likelihood of dementia onset in individuals without dementia. This study aimed to assess the reliability of the ANU-ADRI (Australian National University Alzheimer's Disease Risk Index)-Short Form in Turkish geriatric patients. METHODS: This methodological study involved 339 elderly patients attending the geriatric outpatient clinic for various reasons. The known-group validity and divergent validity were assessed. The ANU-ADRI was administered during the baseline test and again within one week for retest purposes. Alongside the ANU-ADRI, all participants underwent a comprehensive geriatric assessment, including Activities of Daily Living (ADL), mobility assessment (Performance-Oriented Mobility Assessment (POMA) and Timed Up and Go Test), nutritional assessment (Mini Nutritional Assessment (MNA)), and global cognition evaluation (Mini-Mental State Examination (MMSE)). RESULTS: The scale demonstrated satisfactory linguistic validity. A correlation was observed between the mean scores of the ANU-ADRI test and retest (r = 0.997, p < 0.001). Additionally, there existed a moderate negative linear association between the ANU-ADRI and MMSE scores (r = -0.310, p < 0.001), POMA (r = -0.406, p < 0.001), Basic ADL (r = -0.359, p < 0.001), and Instrumental ADL (r = -0.294, p < 0.001). Moreover, a moderate positive linear association was found between the ANU-ADRI and the Timed Up and Go Test duration (r = 0.538, p < 0.001). CONCLUSION: The ANU-ADRI-Short Form was proved as a valuable tool for clinical practice, facilitating the assessment of Alzheimer's disease risk within the Turkish geriatric population.

Validation of the Turkish version of the Lewy body composite risk score.

The Lewy Body Composite Risk Score (LBCRS) has been developed to increase the sensitivity and specificity of the diagnosis attributable to Lewy body pathology outside of specialty centers. We aimed to assess the validity and reliability of the Turkish version of the LBCRS in patients with dementia with Lewy Bodies (DLB) and investigate the discriminative power of the test in Turkish patients with Alzheimer's disease (AD) and DLB, and control group. The sample population (n = 512) comprised DLB (n = 113), DLB-Mild Cognitive Impairment (MCI)(n = 12), AD (n = 42), AD-MCI (n = 21), and control group (n = 324). A significant group difference was observed in the Turkish version of the LBCRS scores of the five groups (p < .001). The Cronbach's α value was 0.82 (95% CI: 0.799-0.868). The test-retest reliability score of the scale was r = 0.94 and p < .001. The subscales of the LBCRS (motor and nonmotor subdomains of the disease) were determined to explain 65.961% of the total variance with an eigenvalue >1. In patients with DLB, the cutoff score of ≥3 showed sensitivity (92%) and specificity (81%) (area under the curve [AUC] = 0.883, 95% CI: 0.815-0.951), p < .001) compared with the AD. Compared to the control group, the cutoff score of ≥3 showed a sensitivity of 98% and specificity of 97% (AUC = 0.994, 95% CI: 0.989-0.999, p < .001). The Turkish version of LBCRS permits accurate diagnosis of DLB with high sensitivity and specificity. Also, it can be useful to inform the caregivers regarding the course of the disease during the follow-up.

Neuroleptic Malignant Syndrome in Patients With Dementia: Experiences of A Single Memory Clinic.

OBJECTIVES: Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course. METHODS: The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay. RESULTS: Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died. CONCLUSIONS: This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.

Muscle Strength Seems to be Related to The Functional Status and Severity of Dementia in Older Adults with Alzheimer's Disease.

AIM: This study aimed to determine the possible interrelationships between sarcopenia and Alzheimer's disease (AD). BACKGROUND: Sarcopenia and AD are two common geriatric syndromes; however, the relationship between AD and sarcopenia has not been evaluated in detail so far. OBJECTIVE: The objective is to evaluate the relationship between AD and sarcopenia. METHODS: This cross-sectional study was performed retrospectively on 128 patients with probable AD, with a mean age of 76.56±7.54 years. Comprehensive Geriatric Assessment, including the activities of daily living (ADLs), malnutrition, frailty, mini-mental state examination (MMSE), and orthostatic hypotension was performed. Sarcopenia was defined according to the revised EWGSOP-2 criteria. RESULTS: The frequency of probable sarcopenia and definitive sarcopenia was 54.7% and 18.7%, respectively. AD patients with probable sarcopenia had lower MMSE and ADLs scores and were frailer. Clinical dementia rating (CDR) score, MMSE, and basic and instrumental ADLs were independently related to probable sarcopenia in the patients (p=0.003, p<0.001, p=0.001, and p=0.001, respectively). The prevalence of probable sarcopenia in those with CDR 2 was higher than in those with CDR 0.5 and 1 (p=0.002). CONCLUSION: Our findings suggest that probable sarcopenia seems to be related to worse MMSE and ADLs scores and frailty in patients with AD and seems to be related to the severity of AD. Considering adverse health outcomes and the burden of sarcopenia on the patients and their caregivers, optimal care and treatment of sarcopenia in patients with AD are of great importance.

Hyperuricemia may be associated with muscle wellness in older adults.

PURPOSE: Sarcopenia, associated with morbidity and mortality, is a common geriatric syndrome in older adults. In this study, we investigated the relationship between uric acid, which is a powerful antioxidant and has intracellular proinflammatory activity, and sarcopenia in older adults. METHODS: This is a cross-sectional retrospective study involving a total of 936 patients. The diagnosis of sarcopenia was evaluated based on the EGWSOP 2 criteria. The patients were divided into two groups according to hyperuricemia (for females > 6 mg/dl, for males > 7 mg/dl); hyperuricemia and control. RESULTS: The frequency of hyperuricemia was 65.40%. Patients with hyperuricemia were older than the control group and female gender frequency was higher (p = 0.001, p < 0.001, respectively). Sarcopenia was negatively associated with hyperuricemia as a result of the adjustment analysis made according to demographic characteristics, comorbidities, laboratory results, malnutrition, and malnutrition risk. (p = 0.034). Besides, muscle mass and muscle strength were associated with hyperuricemia (p = 0.026 and p = 0.009, respectively). CONCLUSIONS: Considering the positive effect of hyperuricemia on sarcopenia, avoiding aggressive uric acid-lowering therapy may be a good option in older adults with asymptomatic hyperuricemia.

The applause sign in elderly patients with idiopathic normal pressure hydrocephalus.

Applause sign (AS) was shown to be an indicator of frontal subcortical dysfunction in many neurodegenerative diseases. Idiopathic normal pressure hydrocephalus (INPH) is one of those in which frontosubcortical disconnection can be displayed. We aimed to examine the presence of AS in the elderly patients with INPH and its possible diagnostic role in the frontal dysfunction commonly seen in the disease. Sixty-six patients diagnosed with probable INPH, 32 with behavioral variant of frontotemporal dementia (bvFTD) and 325 healthy elderly subjects were included in this cross-sectional and retrospective study. AS was evaluated with the clapping test. Patients with INPH were further assessed with frontal assessment battery (FAB), Stroop test, verbal fluency test and clock drawing test (CDT). The concentration of total amyloid-ß 42 (Aß42), Aß40, total (t) tau and phosphorylated (p)-tau proteins were also measured in the cerebrospinal fluid (CSF). AS was observed in all groups (40% in bvFTD, 28.8% in INPH, 1.2% in controls, respectively). It was significantly more frequent in patients with bvFTD and INPH as compared to the controls (p < 0.001, for each). The frequency was similar in the patients with bvFTD and INPH (p = 0.802). Significant differences were found between the AS(+) and (-) INPH patients with regards to FAB, Stroop test-errors and verbal fluency test, except for the CSF proteins. AS can be used as a simple, useful and rapid clinical test that investigates executive dysfunction in elderly patients with INPH in both inpatient and outpatient settings.

Theracurmin Supplementation May be a Therapeutic Option for Older Patients with Alzheimer's Disease: A 6-Month Retrospective Follow-Up Study.

BACKGROUND: Alzheimer's Disease (AD) is still a great global challenge and agents with various mechanisms represent a promising therapeutic opportunity. Theracurmin, a very highly absorbable curcumin formulation, was shown to improve memory and attention in non-demented people. OBJECTIVE: The aim of the study was to investigate the effect of Theracurmin on disease course in elderly patients with mild cognitive impairment (MCI) and AD. METHODS: This follow-up study was performed retrospectively on 93 patients with MCI or AD. All patients underwent comprehensive geriatric assessment, including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), clock-drawing test, activities of daily living (ADL), at baseline and at the end of the 6th month. 19 patients with AD and 17 with MCI were treated with Theracurmin 180 mg/day per oral. RESULTS: MMSE, MOCA and instrumental ADL scores decreased in AD patients not treated with Theracurmin (p<0.001, p=0.011, and p=0.004, respectively), whereas these scores remained stable in those treated with Theracurmin. This stabilization in the instrumental ADL was also observed in MCI patients treated with Theracurmin. During the follow-up, three MCI patients who did not receive Theracurmin progressed to AD, whereas only one patient progressed in those who received it. CONCLUSION: Theracurmin seems to be a therapeutic option for elderly patients with AD and MCI via providing stabilization of the disease course by preventing progressive loss in cognitive functions and ADLs.

Natural history of ROHHAD syndrome: development of severe insulin resistance and fatty liver disease over time.

BACKGROUND: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare syndrome with unknown etiology. Metabolic abnormalities are not known to be part of the syndrome. We present one of the oldest cases reported in the literature, who developed severe metabolic abnormalities and hepatic disease suggesting that these features may be part of the syndrome. CASE PRESENTATION: A 27-year-old woman, diagnosed with ROHHAD syndrome at age 15, who previously developed diabetes insipidus, growth hormone deficiency, hyperprolactinemia, and hypothyroidism in her first decade of life. This was followed by insulin resistance, NAFLD, liver fibrosis, and splenomegaly before age 14 years. Her regimen included a short course of growth hormone, and cyclic estrogen and progesterone. Her metabolic deterioration continued despite treatment with metformin. Interestingly, she had a favorable response to liraglutide therapy despite having a centrally mediated cause for her obesity. At age 26, a 1.6 cm lesion was found incidentally in her liver. Liver biopsy showed hepatocellular carcinoma which was successfully treated with radiofrequency ablation. CONCLUSION: Metabolic abnormalities, Insulin resistance and fatty liver disease are potentially part of the ROHHAD syndrome that may develop over time. GLP1 agonists were reasonably effective to treat insulin resistance and hyperphagia. Patients with ROHHAD may benefit from close follow up in regards to liver disease.