Clinical Neuroscience

Cholinesterase inhibitors and memantine for the treatment of Alzheimer and non-Alzheimer dementias

BALÁZS Nóra 1, BERECZKI Dániel1,2, KOVÁCS Tibor 1,2

NOVEMBER 30, 2021

Clinical Neuroscience - 2021;74(11-12)

DOI: https://doi.org/10.18071/isz.74.0379

Review

Szöveg nagyítása:

-
+

In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients’ and caregivers’ quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer’s therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer’s dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer’s and non-Alzheimers’s dementias.

AFFILIATIONS

  1. Semmelweis University, Department of Neurology, Budapest
  2. MTA-SE Neuroepidemiological Research Group ELKH, Budapest

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Clinical Neuroscience

Atypical presentation of late-onset Sandhoff disease: a case report

SALAMON András , SZPISJAK László , ZÁDORI Dénes, LÉNÁRT István, MARÓTI Zoltán, KALMÁR Tibor , BRIERLEY M. H. Charlotte, DEEGAN B. Patrick , KLIVÉNYI Péter

Sandhoff disease is a rare type of hereditary (autosomal recessive) GM2-gangliosidosis, which is caused by mutation of the HEXB gene. Disruption of the β subunit of the hexosaminidase (Hex) enzyme affects the function of both the Hex-A and Hex-B isoforms. The severity and the age of onset of the disease (infantile or classic; juvenile; adult) depends on the residual activity of the enzyme. The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. Detailed neurological examination revealed mild symmetrical weakness in the hip flexors without the involvement of other muscle groups. The patellar reflex was decreased on both sides. Laboratory tests showed no relevant alteration and routine electroencephalography and brain MRI were normal. Nerve conduction studies and electromyography revealed alterations corresponding to sensory neuropathy. Muscle biopsy demonstrated signs of mild neurogenic lesion. Her younger brother (32-year-old) was observed with similar symptoms. Detailed genetic study detected a known pathogenic missense mutation and a 15,088 base pair long known pathogenic deletion in the HEXB gene (NM_000521.4:c.1417G>A; NM_000521:c.-376-5836_669+1473del; double heterozygous state). Segregation analysis and hexosaminidase enzyme assay of the family further confirmed the diagnosis of late-onset Sandhoff disease. The purpose of this case report is to draw attention to the significance of late-onset Sandhoff disease amongst disorders presenting with proximal predominant symmetric lower limb muscle weakness in adulthood.

Clinical Neuroscience

[Relationships between COVID-19 disease, nutritional status, and dysphagia, particularly in stroke patients ]

KOVÁCS Andrea, SZABÓ Pál Tamás, FOLYOVICH András

[The new coronavirus, SARS-CoV-2, which causes the COVID-19 disease can lead to severe acute respiratory distress syndrome (ARDS). It poses a serious challenge to the health care system, especially intensive care. Neurological patients, usually of advanced age and with a myriad of comorbidities, are at particular risk through the impact of the new coronavirus on their condition and nutritional capacity. Stroke is a leader in morbidity and mortality data, with a focus on dysphagia and its complications due to COVID-19 disease and acute cerebrovascular accident. In the acute phase of stroke, 30-50% of patients suffer from dysphagia, which still shows a prevalence of 10% six months later. Dysphagia results in decreased or insufficient fluid and nutrient uptake, supp­lemented by inactivity, leading to malnutrition and sarcopenia, which worsens overall condition, outcome, and rehabilitation efficiency. Screening and early detection of swallowing disorders is a fundamental issue in order to develop a personalized and timely-initiated nutritional therapy strategy. Nutritional therapy plays a key role in frequent intensive care due to COVID-19 disease, where it increases the chances of recovery and reduces the length of stay in the intensive care unit and mortality. This is especially true in critically ill patients requiring prolonged ventilation. In COVID-19 diagnosed patients, screening for dysphagia, bedside assessment, and instrumental examination, followed by swallowing rehabilitation, are of paramount importance. Stroke can also be a complication of the COVID-19 infection. Care for cerebrovascular patients has also adapted to the pandemic, “triazination” has become systemic, and dysphagia screening for stroke patients and nutritional therapy adapted to it have also shed new light. ]

Clinical Neuroscience

[Effective therapy in highly active pediatric multiple sclerosis ]

MERÔ Gabriella, MÓSER Judit, LIPTAI Zoltán, DIÓSZEGHY Péter, BESSENYEI Mónika, CSÉPÁNY Tünde

[Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un­der the age of 16 formerly known as “early-onset multiple sclerosis” or “juvenile multiple sclerosis”, seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter­feron β-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients’ treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.]

Clinical Neuroscience

Rare complication of West Nile viral encephalitis

FARAGÓ Péter , FRICSKA-NAGY Zsanett, KLIVÉNYI Péter , TAJTI János

In our case report, we are presenting a 72 years old male patient. The patient’s symptoms were fever, dizziness, general weakness at the time of admission. The laboratory and CSF tests revealed central nervous system inflammation. West Nile virus was identified from the cerebrospinal fluid. After the symptoms of infection and during supporting treatment, severe, progressing hyponatremia evolved with unknown pathology. According to previous investigations and our diagnostic and therapeutic algorithm cerebral salt wasting syndrome identified as occasion.

All articles in the issue

Related contents

Clinical Neuroscience

The effects of ultra-early clipping on survival and neurological outcome in poor-grade aneurysmal subarachnoid haemorrhage

ŞIMSEK Osman, AKINCI Tolgay Ahmet

European Stroke Organisation guidelines advise treating aneurysmal subarachnoid haemorrhage (aSAH) as early as possible. However, the optimum timing along with its beneficial effects is controversial. Therefore, we aimed to investigate the effects of ultra-early clipping on neurological outcomes and survival in poor-grade aneurysmal subarachnoid haemorrhages.

This retrospective study included all poor-grade aneurysmal subarachnoid haemorrhage patients treated by ultra-early surgical clipping at Trakya University Hospital between January 1, 2001, and December 31, 2020. We analysed the outcome and mortality data of these patients. Specifically, we evaluated the effects of ultra-early clipping on outcomes, defined as within six hours of the onset of symptoms.

From 813 records, 212 met our inclusion criteria. Of these, 117 (55.2%) were female and 95 (44.8%) male. The mean age was 58.3 ± 13.7 years. Glasgow Outcome Scale scores differed significantly between age groups, subarachnoid haemorrhage grades, those who did and did not rebleed, and those who did or did not suffer from vasospasms. A beneficiary relationship was found between ultra-early clipping and mortality among patients. Furthermore, favourable outcomes were significantly more frequent in the ultra-early clipping group.

The aSAH patients treated at our hospital who received ultra-early clipping had significantly lower mortality rates and more favourable outcomes. The difference was significant among those treated during the last decade and among patients younger than 50.

Clinical Neuroscience

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

Clinical Neuroscience

[Treatment of complex regional pain syndrome with amitriptyline]

KOMOLY Sámuel

[Introduction - Complex regional pain syndrome is a di­stressing neuropathic pain condition without known etiology and evidence based treatment. Case presentation - Here a posttraumatic severe case of complex regional pain syndrome is presented, successfully treated by amitriptyline monotherapy. Amitriptyline is one of the most effective evidence based treatments of peri­pheral diabetic neuropathic pain and other neuropathic pain syndromes. Discussion - Amitriptyline seems to be effective to decrease pain, autonomic and motor symptoms in chronic regional pain syndrome. Conclusion - Controlled trials may be warranted to test the effectiveness of amitriptyline in complex regional pain syndrome.]

Clinical Neuroscience

[Verbal Episodic Memory Test]

RACSMÁNY Mihály, PAJKOSSY Péter, SZANDRA László, SZŐLLŐSI Ágnes

[The decline of episodic memory is one of the earliest cognitive markers of mild cognitive impairment and various types of dementia. Until today, however, there is no standardized Hun­garian episodic memory test that takes into account the characteristics of the Hungarian language. The study presents the structure and standardized use of a new memory test (Verbal Episodic Memory Test, VEMT) as well as normative data in Hungary. 

The VEMT is suitable for the comprehensive examination of verbal learning abilities in a broader sense, and more specifically, for the neuropsychological measurement of verbal list learning abilities. In the present study, we constructed a normative database consisting of data from 385 participants.

We showed that the VEMT is sensitive to demographic factors (e.g., age) which are linked to differences in episodic memory performance. Open access to the test is provided, and the normative scores are presented as well. 

The indicators of the test are suitable for drawing a learning curve, for showing the interaction of new and previously learned information (interference effects), and for measuring differences between free recall and cued recall. Furthermore, the test scores are appropriate for distinguishing the effects of different types of memory encoding forms (phonological, semantic, and episodic), for measuring the ability to reconstruct the presentation of a sequence (memory order information), for detecting the rate of forgetting, for measuring recognition abilities, and for detecting hippocampus-related mnemonic pattern separation and completion functions. ]

Clinical Neuroscience

Personality traits and psychological complaints under patients suffering from headaches

HAL Melinda , HAL Viktor , VÉCSEI László , BALOG Anna , MAJLÁTH Zsófia , TAJTI János, ERTSEY Csaba , BOZSIK György , ZSOMBÓK Terézia , PUREBL György

Although headaches are often comorbid with psychological symptoms, the underlying psychological processes, e.g. the role of personality dimensions as headache determinants remains unclear. Studies found associations between headaches and various personality traits; according to the Big Five model of personality, persons suffering from headaches exhibit a higher rate in neuroticism, while a lower rate in extraversion, openness to experiences and positive emotions.