Mental Health among Geriatric Healthcare Workers in Italy during the COVID-19 Pandemic: Results from a National Survey.

OBJECTIVES: This study aimed to investigate the psychological impact of the COVID-19 pandemic on healthcare workers (HCWs) in geriatric settings. DESIGN: Online cross-sectional survey. SETTINGS AND PARTICIPANTS: 394 geriatric HCWs in Italy. MEASUREMENTS: The survey was developed by a multidisciplinary team and disseminated in April 2022 to the members of two geriatric scientific societies (Italian Society of Geriatrics and Gerontology and Italian Association of Psychogeriatrics). The survey examined the experiences related to the COVID-19 pandemic, as well as psychological burden and support. Work-related anxiety and distress related to the pandemic were studied using the SAVE-9 scale (Stress and Anxiety to Viral Epidemics). RESULTS: Three hundred sixty-four participants (92.4%) changed their job activity during the pandemic and about half (50.9%) failed to cope with this change, 58 (14.7%) had increased work-related anxiety, and 39 (9.9%) work-related stress levels. Three hundred forty (86.3%) participants reported acute stress reaction symptoms, including irritability, depressed mood, headache, anxiety, and insomnia, and 262 (66.5%) required psychological support, mainly from friends/relatives (57.9%) and/or colleagues (32.5%). Furthermore, 342 participants (86.8%) recognized they would benefit from informal and formal psychological support in case of future similar emergencies. CONCLUSIONS: This study highlights the high psychological burden experienced by geriatric HCWs in Italy during the COVID-19 pandemic and emphasizes the need for supportive interventions.

Clinical Presentation of COVID19 in Dementia Patients.

OBJECTIVE: No studies analyzing the role of dementia as a risk factor for mortality in patients affected by COVID-19. We assessed the prevalence, clinical presentation and outcomes of dementia among subjects hospitalized for COVID19 infection. DESIGN: Retrospective study. SETTING: COVID wards in Acute Hospital in Brescia province, Northern Italy. PARTICIPANTS: We used data from 627 subjects admitted to Acute Medical wards with COVID 19 pneumonia. MEASUREMENTS: Clinical records of each patients admitted to the hospital with a diagnosis of COVID19 infection were retrospectively analyzed. Diagnosis of dementia, modalities of onset of the COVID-19 infection, symptoms of presentation at the hospital and outcomes were recorded. RESULTS: Dementia was diagnosed in 82 patients (13.1%). The mortality rate was 62.2% (51/82) among patients affected by dementia compared to 26.2% (143/545) in subjects without dementia (p<0.001, Chi-Squared test). In a logistic regression model age, and the diagnosis of dementia resulted independently associated with a higher mortality, and patients diagnosed with dementia presented an OR of 1.84 (95% CI: 1.09-3.13, p<0.05). Among patients diagnosed with dementia the most frequent symptoms of onset were delirium, especially in the hypoactive form, and worsening of the functional status. CONCLUSION: The diagnosis of dementia, especially in the most advanced stages, represents an important risk factor for mortality in COVID-19 patients. The clinical presentation of COVID-19 in subjects with dementia is atypical, reducing early recognition of symptoms and hospitalization.

Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation.

The physio-pathologic interrelationships between endothelium and GvHD have been better elucidated and have led to definition of the entity 'endothelial GvHD' as an essential early phase prior to the clinical presentation of acute GvHD. Using the CellSearch system, we analyzed circulating endothelial cells (CEC) in 90 allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients at the following time-points: T1 (pre-conditioning), T2 (pre-transplant), T3 (engraftment), T4 (onset of GvHD) and T5 (1 week after steroid treatment). Although CEC changes in allo-HSCT represent a dynamic phenomenon influenced by many variables (that is, conditioning, immunosuppressive treatments, engraftment syndrome and infections), we showed that CEC peaks were constantly seen at onset of acute GvHD and invariably returned to pre-transplant values after treatment response. Since we showed that CEC changes during allo-HSCT has rapid kinetics that may be easily missed if blood samples are drawn at pre-fixed time-points, we rather suggest an 'on demand' evaluation of CEC counts right at onset of GvHD clinical symptoms to possibly help differentiate GvHD from other non-endothelial complications. We confirm that CEC changes are a suitable biomarker to monitor endothelial damage in patients undergoing allo-transplantation and hold the potential to become a useful tool to support GvHD diagnosis (ClinicalTrials.gov NCT02064972).

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. MATERIAL AND METHODS: Pre-, Intra- and Post-operative data were collected. Tumor necrosis factor (TNF), interleukine 6, procalcitonine (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. RESULTS: Thirty-eight patients included, 29 (76.3%) female. Mean/median PCI: 9.2/5. Primary malignancy: 5 colo-rectal (13.2%), 5 gastric (13.2%), 23 ovarian (60.5%) and 5 others (13.2%). CCR 0-1 reached in all patients. Cardiac Index, Heart rate and Central Venous Pressure, increased during the procedure while Stroke Volume Variation showed a decrease. Mean Arterial Pressure and Superior Vena Cava Oxygenation were stable through the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (p<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (p<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. CONCLUSION: The most significant variations are those of IL-6 and PCT. The cytokines level parallel the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock.

Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation.

Frontotemporal dementia (FTD) is one of the most important neurodegenerative conditions and Granulin (GRN) is one of the major genes associated to the disease. FTD-GRN patients are still orphan for any evidence-based target-therapy approach. Interestingly, it has been recently found that alkalizing agents rescued haploinsufficiency in cellular models expressing FTD-GRN mutations. We set up a pilot phase II clinical trial in five FTD patients with GRN Thr272s(g.1977_1980delCACT) mutation, to determine if amiodarone (200 mg/day) may (1) reverse progranulin deficiency and (2) delay disease progression. Each patient was scheduled for 7 study visits over 12 months period. We assessed GRN levels at baseline and after amiodarone administration during the treatment course. Somatic and neurologic examinations, along with cognitive and behavioral assessment were recorded as well. No significant effect on peripheral GRN levels was observed. In treated FTD, disease course did not differ when compared with a group of untreated FTD-GRN patients. This is the first trial targeting progranulin rescue in FTD-GRN patients using amiodarone. Despite the negative findings, it may be interesting to extend this attempt to a larger sample of subjects and to other alkalizing agents to restore granulin haploinsufficiency.

Personality changes in Alzheimer's disease.

BACKGROUND: Assessment of personality changes in patients with dementia has received little systematic investigation, although caregivers report personality modifications in every phase of dementia. METHODS: A group of 52 patients with probable Alzheimer's disease (AD) vs. a group of fifteen control subjects were selected for these personality tests before and after the manifestation of dementia using an Italian version of Brooks and McKinaly's Personality Inventory (PI). RESULTS: After the onset of AD, a significant shift from positive to negative characteristics in PI was observed in 12 of 18 bipolar pairs of adjectives constituting the instrument and the total mean PI score decreased significantly (p < 0.001), indicating a substantial worsening of personality profile. In the control group however, evaluated before and after retirement, personality traits and total mean PI score did not show a significant change. The association of personality traits and total PI score with demographic, cognitive and functional characteristics of AD patients was calculated. CONCLUSION: Personality changes have been depicted to be influenced by severity of cognitive, functional and behavioural complaints rather than age, sex, education and disease duration. These first applications of the Italian version of PI confirmed that personality modifications make a consistent aspect of the phenomenology of AD although in the negative direction. Further studies are needed to understand the nature of personality changes in dementia and the utility of PI to investigate these changes.

Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study.

Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.

Clinical characteristics and risk factors of delirium in demented and not demented elderly medical inpatients.

OBJECTIVES: to evaluate the differences in clinical characteristics and risk factors of delirium in elderly medical inpatients according to the presence or not of dementia. DESIGN: cross-sectional, observational study. SETTING: acute medical care unit (ACU) of a general hospital. PARTICIPANTS: 330 patients aged 65 and older consecutively admitted on a 24-week period. MEASUREMENTS: Functional status, cognitive abilities, severity of acute illness (Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score), Confusion Assessment Method (CAM), Delirium Rating Scale (DRS) and One Day Fluctuation Scale (ODFS). RESULTS: patients with delirium represent 19.1% of the sample, 41.0% of which had also dementia. Hyperactive form of delirium was 41.0%; hypoactive 11.0% and mixed 48.0%. In non demented patients, the delirious patients showed higher APACHE II score, more severe functional decline, poorer cognitive status respect to not delirious. In demented patients no differences were found in APACHE II score and cognitive status among delirious and not delirious subjects. In this group, functional decline (p = .012), acute infection (p = .007), psychotropic drugs use (p = .028) and severe hypoalbuminemia (p = .036) represented risk factors for the onset of delirium. Demented patients had higher perceptual disturbances (p = .040) and less severe delusions (p = .001), while total DRS score do not differs in the two groups. According to ODFS, delirium episode was more fluctuating in patients with dementia. CONCLUSION: clinical characteristics and risk factors of delirium are different in demented and not demented elderly inpatients. Patients with dementia are vulnerable to delirium at lower levels of medical acuity than non-demented patients.

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). METHODS: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. RESULTS: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

Effects of acetyl-L-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.

Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.

Reality orientation therapy to delay outcomes of progression in patients with dementia. A retrospective study.

OBJECTIVE: To evaluate the impact of continued Reality Orientation Therapy (ROT) in delaying the outcomes of dementia progression. DESIGN: Retrospective study. Data collection was based on review of clinical charts and on telephone interviews performed with patients or primary caregivers. SETTING: Day hospital of the Alzheimer's Disease Unit, Brescia (Italy). SUBJECTS: Seventy-four patients enrolled in at least one cycle of ROT from 1994 to 1998 were studied. INTERVENTIONS: Rehabilitative intervention based on formal ROT. MAIN OUTCOME MEASURES: This study analysed the time to the occurrence of any of the following: cognitive decline on Mini-Mental State Examination scores, urinary incontinence as an index of functional decline, institutionalization, and death. RESULTS: Data on a 30-month period after the first ROT session were analysed. We compared 46 patients (treatment group) who completed from 2 to 10 ROT cycles (corresponding to 8-40 weeks of training; mean = 15.48) with 28 patients (control group) who completed only one ROT cycle (4 weeks). Treatment group showed higher estimated survival rates than control group on cognitive decline (p = 0.022) and institutionalization (p = 0.002). The relative risks for cognitive decline and institutionalization in the control group compared with treatment group were 0.60 (p = 0.014), and 0.42 (p = 0.021), respectively. CONCLUSIONS: Continued ROT classes during the early to middle stages of dementia may delay nursing home placement and slow down the progression of cognitive decline.

Clinical aspects of Alzheimer's disease.

Alzheimer's disease (AD) is the most common of the dementing disorders. AD begins insidiously and progresses gradually; it is characterized clinically not only by an impairment in cognition, but also by a decline in global function, a deterioration in the ability to perform activities of daily living, and the appearance of behavioral disturbances. No definitive tests for the diagnosis are available, and AD is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies. Disease progression is highly variable, and median survival after the onset of dementia ranges from 5 to 9.3 years. Early recognition of AD allows time to plan for the future, and to treat patients before marked deterioration occurs.

The Itel-MMSE: an Italian telephone version of the Mini-Mental State Examination.

METHOD: We compared performance in an Italian telephone version of the Mini-Mental Status Examination (Itel-MMSE) with performance in the standard MMSE administered face to face to 104 inpatients affected by cognitive deficit. RESULTS: Their cognitive ability varied from mildly to severely impaired. Total scores of the two MMSE versions correlated strongly for all patients (r=0.85) and for very mildly (r=0.77), mildly (r=0.79), and moderately (r=0.72) demented. A weak but statistically significant correlation was observed for severely demented patients (r=0.46). The study establishes the validity and reliability of the Itel-MMSE as well as between rater and test-retest reliability. We calculated a regression equation for use in predicting MMSE scores from Itel-MMSE scores. Data fit a linear regression model.

Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study.

BACKGROUND: Magnetic resonance imaging (MRI) of hippocampal atrophy is a sensitive but not specific method to support the clinical diagnosis of early Alzheimer's disease (AD). We recently described our findings that atrophy of the entorhinal cortex (ERC) in frontotemporal dementia (FTD) is equal to that found in AD but that hippocampal atrophy in FTD is less than that found in AD. The MRI volumes of these structures provide a topographic representation of the region of interest. We hypothesized that two different dementias with distinct histopathologic and clinical features might, in addition to quantitative patterns, display topographically different patterns of atrophy. METHODS: We adopted a morphometric approach to monitor the pattern of atrophy of the hippocampus and the ERC by computing two-dimensional profiles from MRI volumes of the structures in control subjects and patients with FTD and AD. RESULTS: Compared with control subjects, atrophy of the hippocampus in patients with AD was diffuse. In patients with FTD, atrophy of the hippocampus was localized predominantly in the anterior hippocampus, suggesting a different pattern of hippocampal atrophy in FTD compared with AD. The amount and pattern of atrophy of the entorhinal cortex was virtually equal in both demented groups. CONCLUSIONS: This study provides novel data on the nature of medial temporal lobe atrophy in FTD. Morphometric MRI may be a useful technique for characterizing different patterns of atrophy in primary degenerative dementias in vivo.