Special Issue "Personalized Medicine for Neurodegenerative Dementia"

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (5 July 2023) | Viewed by 22279

Special Issue Editor

1. Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, 00179 Rome, Italy
2. Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA
Interests: dementia; neuropsychiatry; neuropsychology; neuroimaging; schizophrenia; mood disorders; genetics; neuroinflammation; movement disorders; neurodegeneration; childhood trauma

Special Issue Information

Dear Colleagues,

Neuropsychiatric symptoms/disorders in neurodegenerative dementias (i.e., Alzheimer's Disease, Lewy Body Disease, Fronto-temporal Dementia, Parkinson's Disease and Atypical parkinsonisms) are a group of heterogeneous clinical manifestations. Epidemiology and phenomenology are highly variable depending, among the others, on the specific diagnosis, type of assessment, phases of the illness and associated biomarkers and polytherapy. The extreme variability of treatment response and side effects make the management of the neuropsychiatric phenomena associated with neurodegenerative dementias difficult and make of greatest importance the personalized medicine approach

Prof. Dr. Gianfranco Spalletta
Guest Editor

Manuscript Submission Information

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Keywords

  • Dementia
  • mild cognitive impairment
  • subjective cognitive complaint
  • neurodegeneration
  • risk factors
  • biomarkers
  • early diagnosis
  • treatment
  • neuropsychiatry
  • Alzheimer’s disease
  • frontotemporal dementia
  • Lewy body disease
  • Parkinson’s disease dementia
  • progressive supranuclear palsy
  • cortico-basal degeneration
  • mood disorder
  • depression
  • apathy
  • psychosis
  • anxiety
  • impulsivity
  • aggression
  • aberrant motor behavior

Published Papers (9 papers)

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Research

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Article
Effects of a Cognitive Stimulation Program in Institutionalized Patients with Dementia
J. Pers. Med. 2022, 12(11), 1808; https://doi.org/10.3390/jpm12111808 - 01 Nov 2022
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Abstract
Background: The advances achieved by the available research that focus on understanding memory operation and cognitive functions have helped the development of specific treatment approaches. These can help to maintain or improve the cognitive function and well-being of people with dementia. The use [...] Read more.
Background: The advances achieved by the available research that focus on understanding memory operation and cognitive functions have helped the development of specific treatment approaches. These can help to maintain or improve the cognitive function and well-being of people with dementia. The use of cognitive stimulation in dementia has a long history. There are multiple studies that have demonstrated its benefits on the cognitive levels of patients with mild to moderate dementia. However, all of the studies on this type of non-pharmacological intervention conclude that there is a need for more clinical trials in order to give more solidity to the evidence already found. The objective of this pilot study was to assess the effects of an occupational therapy cognitive training program on the cognitive function of institutionalized older adults with dementia. Methods: The study was a pilot randomized clinical controlled trial. A total of 58 participants with major neurocognitive disorder or dementia were randomized to the occupational therapy cognitive training program group or to the conventional occupational therapy group twice a week for 5 weeks. The cognitive level was measured with the Global Deterioration Scale (GDS) and the Lobo’s Cognitive Mini Test (LCMT), which is the Mini-Mental Status Examination in Spanish. Measures were taken at baseline (week 0), after 5 weeks of treatment (week 5), and after 6 weeks of follow up (week 12). A value of p < 0.05 was considered as statistically significant. Results: There were no statistical differences between groups in the LCMT global scores at baseline or after the intervention at week 5. However, the analysis of the specific cognitive areas assessed in the Lobo’s Cognitive Mini Test indicated that that the intervention group significantly improved comprehension of verbal commands and praxis (p = 0.021). At the follow-up measure, the differences obtained in relation to verbal commands and praxis maintained the statistical differences significantly (p = 0.009). Conclusions: Occupational therapy based on cognitive training shows positive effects on the maintenance of the global cognitive state of institutionalized older adults with dementia and improves significantly the comprehension of verbal commands and praxis. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Article
Association between Late-Onset Ménière’s Disease and the Risk of Incident All-Cause Dementia
J. Pers. Med. 2022, 12(1), 19; https://doi.org/10.3390/jpm12010019 - 31 Dec 2021
Cited by 6 | Viewed by 1266
Abstract
Studies reported an association between impaired hearing and vestibular function with the risk of dementia. This study investigated the association between Ménière’s disease (MD) and the risk of dementia using a nationwide cohort sample of data obtained from the South Korea National Health [...] Read more.
Studies reported an association between impaired hearing and vestibular function with the risk of dementia. This study investigated the association between Ménière’s disease (MD) and the risk of dementia using a nationwide cohort sample of data obtained from the South Korea National Health Insurance Service. The MD group (n = 496) included patients aged over 55 years and diagnosed between 2003 and 2006. The comparison group was selected using propensity score matching (n = 1984). Cox proportional hazards regression models were used to calculate incidence and hazard ratios for dementia events. The incidence of dementia was 14.3 per 1000 person–years in the MD group. After adjustment for certain variables, the incidence of dementia was higher in the MD group than in the comparison group (adjusted hazard ratio (HR) = 1.57, 95% confidence interval = 1.17–2.12). Subgroup analysis showed a significantly increased adjusted HR for developing Alzheimer’s disease (1.69, 95% confidence interval = 1.20–2.37) and vascular dementia (1.99, 95% confidence interval = 1.10–3.57) in the MD group. Patients with dementia experienced a higher frequency of MD episodes than those without dementia. Our findings suggest that late-onset MD is associated with an increased incidence of all-cause dementia, and it might be used as a basis for an earlier diagnosis of dementia. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Article
Precision Medicine into Clinical Practice: A Web-Based Tool Enables Real-Time Pharmacogenetic Assessment of Tailored Treatments in Psychiatric Disorders
J. Pers. Med. 2021, 11(9), 851; https://doi.org/10.3390/jpm11090851 - 27 Aug 2021
Cited by 3 | Viewed by 2464
Abstract
The management of neuropsychiatric disorders involves different pharmacological treatments. In order to perform efficacious drug treatments, the metabolism of CYP genes can help to foresee potential drug–drug interactions. The NeuroPGx software is an open-source web-based tool for genotype/diplotype/phenotype interpretation for neuropharmacogenomic purposes. The [...] Read more.
The management of neuropsychiatric disorders involves different pharmacological treatments. In order to perform efficacious drug treatments, the metabolism of CYP genes can help to foresee potential drug–drug interactions. The NeuroPGx software is an open-source web-based tool for genotype/diplotype/phenotype interpretation for neuropharmacogenomic purposes. The software provides information about: (i) the genotypes of evaluated SNPs (single nucleotide polymorphisms); (ii) the main diplotypes in CYP genes and corresponding metabolization phenotypes; (iii) the list of neuropsychiatric drugs with recommended dosage adjustment (according to CPIC and DPWG guidelines); (iv) the list of possible (rare) diplotypes and corresponding metabolization phenotypes. The combined application of NeuroPGx software to the OpenArray technology results in an easy, quick, and highly automated device ready to be used in routine clinical practice. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Article
Identifying a Common Functional Framework for Apathy Large-Scale Brain Network
J. Pers. Med. 2021, 11(7), 679; https://doi.org/10.3390/jpm11070679 - 19 Jul 2021
Cited by 4 | Viewed by 1761
Abstract
Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) [...] Read more.
Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) and Parkinson’s disease (PD) compared to a group of healthy controls (HC). The study sample includes a total of 60 subjects: 20 apathetic FTD and PD patients, 20 non apathetic FTD and PD patients, and 20 HC matched for age. Two disease-specific apathy-evaluation scales were used to measure the presence of apathy in FTD and PD patients; in the same day, a 3T brain magnetic resonance imaging (MRI) with structural and resting-state functional (fMRI) sequences was acquired. Differences in functional connectivity (FC) were assessed between apathetic and non-apathetic patients with and without primary clinical diagnosis revealed, using a whole-brain, seed-to-seed approach. A significant hypoconnectivity between apathetic patients (both FTD and PD) and HC was detected between left planum polare and both right pre- or post-central gyrus. Finally, to investigate whether such neural alterations were due to the underlying neurodegenerative pathology, we replicated the analysis by considering two independent patients’ samples (i.e., non-apathetic PD and FTD). In these groups, functional differences were no longer detected. These alterations may subtend the involvement of neural pathways implicated in a specific reduction of information/elaboration processing and motor outcome in apathetic patients. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Article
Cognitive and Neuropsychiatric Profiles in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease
J. Pers. Med. 2021, 11(1), 51; https://doi.org/10.3390/jpm11010051 - 16 Jan 2021
Cited by 9 | Viewed by 2380
Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson’s disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD [...] Read more.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson’s disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD specific characteristics. Thirty-eight patients with iRBD, 38 PD patients with RBD (PD + RBD), 38 PD patients without RBD (PD-RBD) and 38 HC underwent a comprehensive neurological, neuropsychological and neuropsychiatric evaluation. iRBD, PD + RBD and PD-RBD performed worse than HC in short-term verbal memory, praxia, language and executive functions. iRBD had higher levels of anxiety, depression, apathy and alexithymia than HC. iRBD had higher levels of apathy than PD + RBD. Both PD groups had higher levels of anxiety and depression than HC. Surprisingly, iRBD performed better than all groups in long-term verbal memory. Patients diagnosed with iRBD are characterized by poor global cognitive performance, but better long-term memory and higher levels of depression, anxiety, alexithymia and apathy. Alexithymia and apathy in patients diagnosed with iRBD may be the expression of precocious derangement of emotional regulation, subsequently observed also in PD. Cognitive and neuropsychiatric symptoms of iRBD are early clinical manifestations of widespread neurodegeneration. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Article
Subclinical Cognitive and Neuropsychiatric Correlates and Hippocampal Volume Features of Brain White Matter Hyperintensity in Healthy People
J. Pers. Med. 2020, 10(4), 172; https://doi.org/10.3390/jpm10040172 - 15 Oct 2020
Cited by 4 | Viewed by 2558
Abstract
White matter hyperintensities (WMH) are associated with brain aging and behavioral symptoms as a possible consequence of disrupted white matter pathways. In this study, we investigated, in a cohort of asymptomatic subjects aged 50 to 80, the relationship between WMH, hippocampal atrophy, and [...] Read more.
White matter hyperintensities (WMH) are associated with brain aging and behavioral symptoms as a possible consequence of disrupted white matter pathways. In this study, we investigated, in a cohort of asymptomatic subjects aged 50 to 80, the relationship between WMH, hippocampal atrophy, and subtle, preclinical cognitive and neuropsychiatric phenomenology. Thirty healthy subjects with WMH (WMH+) and thirty individuals without (WMH−) underwent comprehensive neuropsychological and neuropsychiatric evaluations and 3 Tesla Magnetic Resonance Imaging scan. The presence, degree of severity, and distribution of WMH were evaluated with a semi-automated algorithm. Volumetric analysis of hippocampal structure was performed through voxel-based morphometry. A multivariable logistic regression analysis indicated that phenomenology of subclinical apathy and anxiety was associated with the presence of WMH. ROI-based analyses showed a volume reduction in the right hippocampus of WMH+. In healthy individuals, WMH are associated with significant preclinical neuropsychiatric phenomenology, as well as hippocampal atrophy, which are considered as risk factors to develop cognitive impairment and dementia. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Review

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Review
Combined Motor and Cognitive Rehabilitation: The Impact on Motor Performance in Patients with Mild Cognitive Impairment. Systematic Review and Meta-Analysis
J. Pers. Med. 2022, 12(2), 276; https://doi.org/10.3390/jpm12020276 - 14 Feb 2022
Cited by 2 | Viewed by 2734
Abstract
Mild cognitive impairment (MCI), a neurodegenerative disease leading to Alzheimer’s disease or dementia, is often associated with physical complaints. Combined physical and cognitive training (PCT) has been investigated to see the effects on cognitive function, but its impact on motor functions and activities [...] Read more.
Mild cognitive impairment (MCI), a neurodegenerative disease leading to Alzheimer’s disease or dementia, is often associated with physical complaints. Combined physical and cognitive training (PCT) has been investigated to see the effects on cognitive function, but its impact on motor functions and activities of daily living has not been explored yet. The combination of physical and cognitive training may be a valuable non-pharmacological intervention that could preserve motor function and quality of life (QoL). We aimed, therefore, to analyze if combined PCT is effective at improving motor performance in patients with an MCI. A systematic electronic literature search and a meta-analysis were conducted. The following criteria were compulsory for inclusion in the study: (1) randomized controlled trial design; (2) combined PCT compared to motor training alone or no intervention; (3) motor outcomes as a study’s end point. Nine articles met the inclusion criteria. Results showed that PCT significantly enhances balance compared to motor training alone (SMD 0.56; 95% CI 0.07 to 1.06; I2 = 59%; 160 participants), whereas a significant improvement was found for mobility in the PCT group when compared to no intervention (MD −1.80; 95% CI −2.70 to −0.90; I2 = 0%; 81 participants). However, there is no evidence that people with MCI experience an increase in gait speed and QoL at the end of their practice sessions. Further investigation with larger samples and a longer period of monitoring after intervention should be undertaken. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Review
Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic
J. Pers. Med. 2020, 10(3), 102; https://doi.org/10.3390/jpm10030102 - 26 Aug 2020
Cited by 19 | Viewed by 4031
Abstract
SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on [...] Read more.
SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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Other

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Systematic Review
Systematic Review on the Mental Health and Treatment Impacts of COVID-19 on Neurocognitive Disorders
J. Pers. Med. 2021, 11(8), 746; https://doi.org/10.3390/jpm11080746 - 29 Jul 2021
Cited by 4 | Viewed by 2575
Abstract
Objectives. The COVID-19 pandemic has had many public health impacts, especially on vulnerable individuals including adults with neurocognitive disorders (NCD). With increasing literature, this systematic literature review aimed to address the mental health effects of COVID-19 on people with NCD in addition to [...] Read more.
Objectives. The COVID-19 pandemic has had many public health impacts, especially on vulnerable individuals including adults with neurocognitive disorders (NCD). With increasing literature, this systematic literature review aimed to address the mental health effects of COVID-19 on people with NCD in addition to examine the impact of the pandemic on treatments/resources for NCD. Methods. A literature search was conducted in the electronic databases of PubMed, PsycINFO, Web of Science and Google Scholar. Studies were included so long as they assessed the mental health or therapeutic effects of COVID-19 on NCD. Results. Among the retrieved articles, 59 met eligibility criteria. First, the pandemic and resulting self-isolation led to many detrimental effects on psychological well-being. Exacerbation and relapses of neurocognitive and behavioral symptoms were observed, as well as emergences of new psychological symptoms (i.e., depression, anxiety). Second, therapeutic and community services for individuals suffering from NCD, such as social support services and outpatient clinics, were disrupted or reduced leading to postponed appointments and evaluations, as well as reduced access to medications. These issues were somewhat palliated with the growth of telemedicine. Conclusions. This systematic review highlights the extent of the effects of the pandemic, and the topics addressed should be taken into consideration by healthcare practitioners, institutions, and policymakers to ensure that proper measures are employed to protect this population from additional harm. Full article
(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)
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