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.

Antidepressant-induced serotonin syndrome in older patients: a cross-sectional study.

BACKGROUND: Widespread prescription of antidepressants and their resulting role in serotonin syndrome (SS) are of great importance for clinical practice in the elderly. This study aims to investigate possible associations of antidepressant drug-induced SS with related variables in these patients. METHODS: A total of 238 older adults using antidepressants were included. Patients who fulfilled the Hunter Serotonin Toxicity Criteria (HSTC) for SS were considered as the clinical groups (mild, moderate, or severe), and those who did not as the control group. We recorded all patients' demographic and clinical characteristics, including age, gender, comorbidity index, number of medications, daily equivalent dose of the relevant antidepressant according to fluoxetine per day, electrocardiogram test results, laboratory results, and management. RESULTS: The mean age of all patients was 75.4 ± 7.6 years and 63.4% were female. Sixty patients had SS, while 178 patients did not. There was a significant difference between those with and without SS in terms of gender, frequency of combination antidepressant therapy, and daily equivalent antidepressant dose (P < 0.05). The most common diagnostic findings in SS patients were tremor and hyperreflexia and 31.7% was mild, and moderate in 68.3% with higher median age and number of medications (P < 0.041). Antidepressants were discontinued in all patients regardless of severity, of whom 71.7% were treated with benzodiazepines and 36.7% with cyproheptadine. After adjusting for age and sex, association with use of SSRI + SNRI, use of any combination therapy, and daily equivalent dose remained significant. CONCLUSIONS: The widespread single or combined use of antidepressants in older adults represents an increased clinical concern for SS and physicians should be aware of this drug-related complication in older patients.

Prediction of probable sarcopenia with an alternative method: plantar flexion strength.

OBJECTIVE: Sarcopenia is a geriatric syndrome characterized by age-related reduction in muscle mass and strength. Assessment of handgrip strength (HGS) is an essential measurement for the diagnosis of sarcopenia; however, disorders affecting upper limb muscles and joints may pose challenges in assessing handgrip strength. Therefore, the present study aimed to show the validity of plantar flexion strength (PFS) in diagnosing probable sarcopenia and investigating the relations between comprehensive geriatric assessment (CGA) and PFS while determining appropriate cutoff values for PFS. METHODS: A total of 304 older participans who underwent CGA were included. The revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP) were used to determine PFS cutoff values for gender groups. Associations between probable sarcopenia and CGA parameters were investigated using PFS cutoffs. RESULTS: The mean age was 74.50 ± 7.10, and 170 of the participants (55.9%) were women. The mean HGS was 14.40 ± 5.63 kg in women and 25.08 ± 8.07 kg in men. The mean PFS were 13.17 ± 3.62 and 14.92 ± 3.86 kg respectively. In females, PFS cutoff with sensitivity/specificity; 0.81/0.60 was set at 14.95 kg (AUC 0.69, 95%CI: 0.611-0.772, p < 0.001). In males, PFS cutoff with sensitivity/specificity; 0.80/0.55 was set at 16.80 kg (AUC 0.68, 95%CI: 0.593-0.772, p < 0.001). Probable sarcopenia identified by GMS was associated with basic living activities, mobility, and frailty after adjusting for age and sex (p < 0.001, p = 0.021, and p = 0.011 respectively). CONCLUSIONS: Probable sarcopenia identified by PFS could be associated with CGA. PFS may be useful for evaluating probable sarcopenia in older adults whose HGS cannot be estimated accurately.

An Increased Anticholinergic Drug Burden Index Score Negatively Affect Nutritional Status in Older Patients Without Dementia.

INTRODUCTION/AIM: Anticholinergic drugs, which have severe central and peripheric side effects, are frequently prescribed to older adults. Increased anticholinergic drug burden is associated with poor physical and cognitive functions. On the other side, the impact of anticholinergics on nutritional status is not elaborated in the literature. Therefore, this study was aimed to investigate the effect of the anticholinergic burden on nutrition. MATERIALS AND METHODS: Patients who underwent comprehensive geriatric assessment (CGA) 6 months apart were included in the study. Patients diagnosed with dementia were excluded because of the difference in the course of cognition, physical performance and nutrition. Nutritional status and global cognition were evaluated using Mini Nutritional Assessment-short form (MNA-SF), Mini-Mental State Examination (MMSE). Anticholinergic drug burden was assessed with the Drug Burden Index (DBI), enabling a precise dose-related cumulative exposure. Patients were divided into three groups according to DBI score: 0, no DBI exposure; 0-1, low risk; and ≥1, high risk. Regression analysis was performed to show the relationship between the difference in CGA parameters and the change in DBI score at the sixth month. RESULTS: A total of 423 patients were included in the study. Participants' mean age was 79.40 ± 7.50, and 68.6% were female. The DBI 0 score group has better MMSE and MNA-SF scores and a lower rate of falls, polypharmacy, malnutrition, and risk of malnutrition in the baseline. Having malnutrition or risk of malnutrition is 2.21 times higher for every one-unit increase in DBI score. Additionally, during the 6-month follow-up, increased DBI score was associated with decreased MNA-SF and MMSE score, albumin. CONCLUSIONS: The harmful effects of anticholinergics may be prevented because anticholinergic activity is a potentially reversible factor. Therefore, reducing exposure to drugs with anticholinergic activity has particular importance in geriatric practice.

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.

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.

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.

Hematological Parameters and Clinical Features in Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Hematological parameters like red cell distribution width (RDW) and mean platelet volume (MPV) were reported to be associated with inflammation, atherosclerosis, and chronic kidney disease (CKD) progression. In this study, we evaluated RDW and MPV along with clinical features in patients with advanced CKD. We also aimed to detect clues for causative relations concerning these parameters, renal function and comorbidities. METHODS: Stage 3-5 CKD patients (627 total) were included (mean age 63.1 years, 48.3% male). Patients with malignancies, cirrhosis, infections, severe anemia, and systemic inflammation were excluded. Patients were evaluated for clinical features and grouped for comparison using median RDW and MPV. Linear regression models were generated to predict potential influences on RDW and MPV. RESULTS: Mean estimated glomerular filtration rate (eGFR) was 27.3 mL/min/1.73m2. Mean Charlson Comorbidity Index (CCI) score was 5.83 ± 2.06. Patients with high RDW (n = 303) were older with higher CRP and CCI, they also had lower eGFR, hemoglobin, and albumin (P < 0.001 for all). Patients with low MPV (n = 311) had lower eGFR, and platelet counts (P = 0.015 and 0.017). eGFR was negatively correlated with RDW after adjusting for age, gender and comorbidities. In a further adjusted model RDW was associated with CRP, CCI, hemoglobin and albumin (P < 0.05 for all), not with eGFR. MPV was positively correlated with eGFR in our adjusted, and fully adjusted regression models (P = 0.003). CONCLUSION: In this study, we found that high RDW is associated with comorbidity burden, anemia, and inflammatory status in patients with advanced CKD. Meanwhile, low MPV seems to be associated with worse renal function.

Cardiac and Blood Pressure Safety of Transdermal Rivastigmine in Elderly Patients With Dementia With Lewy Bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common dementia. Features of DLB include postganglionic cardiac sympathetic denervation and autonomic instability. Rivastigmine therapy, an acetylcholinesterase inhibitor, is widely used in the primary treatment of DLB; however, the cardiovascular safety and tolerability of transdermal rivastigmine needs to be reviewed. OBJECTIVE: To evaluate whether transdermal rivastigmine has an effect on blood pressure, heart rate, and electrocardiography measurements. MATERIALS AND METHODS: A total of 722 patients diagnosed with dementia were retrospectively screened. Fifty-seven of 98 DLB patients who received transdermal rivastigmine treatment with available serial electrocardiography and blood pressure measurements were included in the study. Baseline and follow-up measurements were compared for patients on the 9.5 to 13.3 mg/d rivastigmine dose for at least 4 weeks. RESULTS: The mean age of the patients was 80.77±6.04, and the majority were women (63%). A total of 8 cases with bradycardia and 5 with orthostatic hypotension were detected during follow-up, and rivastigmine patch was stopped in one of those 8 patients due to symptomatic bradycardia. Nonetheless, there was no difference between baseline and follow-up measurements of the patients, including heart rate, cardiac rhythm, electrocardiographic intervals, blood pressure, pulse pressure, and postural blood pressure changes. CONCLUSIONS: Transdermal rivastigmine therapy is not associated with arrhythmogenic or hypotensive effects in the elderly patients with DLB. However, when prescribing transdermal rivastigmine, physicians should pay attention to newly emerging orthostatic hypotension during the follow-up in these patients.

The Relationship Between Dementia Subtypes and Nutritional Parameters in Older Adults.

OBJECTIVES: There are a few studies showing how nutritional parameters are affected according to dementia subtypes. The aim of this study was to compare the parameters characterizing nutritional status and micronutrient levels according to different dementia subtypes. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Four hundred forty outpatients aged 65 years or older. MEASURES: Newly diagnosed patients with dementia, who underwent comprehensive geriatric assessment (CGA), were retrospectively evaluated. The data on CGA including nutritional status (body mass index), Mini-Nutritional Assessment-Short Form, albumin, and micronutrients (vitamin B12, folate, and vitamin D) were recorded. RESULTS: Of the 396 patients, 195 were diagnosed with Alzheimer type dementia, 70 dementia with Lewy body (DLB), 25 with vascular dementia (VaD), 51 with frontotemporal dementia (FTD), and 55 with normal pressure hydrocephalus. The mean age of the study group was 76.87 ± 8.15 years. The prevalence of malnutrition and the risk of malnutrition were 17.17% and 43.18% in patients, with dementia, respectively. The results of ordinal logistic analysis adjusted by age, sex, and all comorbidities, showed that patients with DLB and VaD were more likely to develop malnutrition [odds ratios 6.834 and 5.414, respectively (P < .001)], whereas FTD had a lower risk of developing malnutrition than the other dementia subtypes (odds ratio 2.883, P = .002).There was no difference in terms of other parameters including vitamin B12, folate, and vitamin D (P > .05). CONCLUSIONS: and Implication: There is a close relationship between dementia and malnutrition. Clinical approaches to minimize malnutrition in persons with dementia should include regular screening for malnutrition and its risk factors, avoidance of dietary restrictions, and support of persons at risk for malnutrition with oral nutritional supplements. Moreover, the influence of nutritional status varies in different types of dementia. Nutritional status may be worse in DLB and VaD compared with other types of dementia, whereas nutritional status in FTD is less.

Postural blood pressure changes in the elderly: orthostatic hypotension and hypertension.

OBJECTIVES: Orthostatic hypotension is a well-known disorder, but orthostatic hypertension (OHT) still remains unclear in older adults. The aim of this study was to determine the comparison orthostatic hypotension with OHT according to fall risk and geriatric assessment parameters. METHODS: A total of 741 patients who were admitted to the geriatric clinic and underwent comprehensive geriatric assessment were reviewed. Orthostatic blood pressure changes were measured by head-up-tilt Table test within the first three minutes. Orthostatic hypotension was defined as 20 or 10-mmHg drop in systolic and/or diastolic blood pressure from supine to standing position. OHT was defined as an increase in systolic blood pressure of 10 mmHg or more while the patient was standing up from the supine position. RESULTS: The mean age was 75 ± 8 and 65. About 65% of all participants were female. The rate of orthostatic hypotension and OHT was 17.3 and 7.2%, respectively. The falls and dementia were more frequent, and the Instrumental Activities of Daily Living (IADL) score was lower in orthostatic hypotension group than in OHT and control groups (P < 0.05). These variables were similar between OHT and control groups (P > 0.05). The rates of falls [odds ratio (OR) = 2.02; 95% confidence interval (CI), (0.94-4.33); P = 0.044] and dementia [OR = 2.65; 95% CI, (1.08-6.48); P = 0.032] in orthostatic hypotension group were still higher than in OHT group, even after adjusting for age, sex, estimated glomerular filtration rate and drugs. CONCLUSION: Orthostatic hypotension may be more significant in terms of falls, dementia and impaired IADLs scores in older adults than in OHT and control groups. It seems that OHT may be of no clinical importance in geriatric practice.

The Effect of Theracurmin on Cognitive Function in an Older Patient with Chemobrain.

Chemobrain is one of the problems that may arise during or after treatment and there is currently no specific treatment for this condition. Our case was a 76-year-old female patient who presented to our clinic with complaints of forgetfulness that did not affect daily living activities for the last year. Breast cancer was diagnosed in 2013 and she has been receiving anastrozole treatment for 6 years after local mass excision surgery and radiotherapy. After a comprehensive geriatric evaluation, cognitive impairment due to systemic cancer therapy was detected and treatment was started with Theracurmin 90 mg twice a day therapy. After 3-months of Theracurmin therapy, she had no cognitive improvement during the follow-up. This case report demonstrated that Theracurmin treatment may be a new option for chemobrain.

The Relationship between the Most Common Subtypes of Dementia and Orthostatic Hypotension in Older Adults.

BACKGROUND: It is crucial to evaluate the causes of morbidity and mortality in elderly patients with dementia, such as orthostatic hypotension (OH), which may affect their daily life activities, reduce the quality of life, and increase the caregiver burden. OBJECTIVE: We aimed to investigate the relationship between OH and the most common subtypes of dementia in detail. METHODS: A total of 268 older adults with dementia diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and behavioral variant frontotemporal dementia (bvFTD), and 539 older adults without dementia were included in this prospective study. Comprehensive geriatric assessment including comorbidity, medication evaluation, and the head-up tilt test was also performed. RESULTS: Of the participants, 13.8, 8.3, 6.4, and 4.8% had AD, DLB, bvFTD, and VaD, respectively. After adjusting for age, gender, the presence of comorbidities, and usage of OH-induced drugs; AD, DLB, and VaD were associated with OH (odds ratio [OR]: 2.23 confidence interval [CI] 95% 1.31-3.80; p = 0.003; OR: 3.68 CI 95% 1.98-6.83; p < 0.001, and OR: 3.56 CI 95% 1.46-8.69; p = 0.005, respectively). Furthermore, VaD was independently related to diastolic OH (OR: 4.19 CI 95% 1.66-10.57; p = 0.002), whereas AD and DLB were not. CONCLUSIONS: This study shows that elderly patients with DLB, AD, and VaD often have OH, a disabling autonomic dysfunction feature. Moreover, diastolic OH may play a role in the development of VaD. Therefore, considering potential complications of OH, it is essential to evaluate OH in the follow-up and management of those patients.