Is MCI really just early dementia? A systematic review of conversion studies

OBJECTIVES: Older people commonly present with memory loss although on assessment are not found to have a full dementia complex. Previous studies have suggested however that people with subjective and objective cognitive loss are at higher risk of dementia. We aimed to determine from the literature the rate of conversion from mild cognitive impairment to dementia. METHODS: Systematic review of MedLine, PsychLit and EmBase. RESULTS: We identified 19 longitudinal studies published between 1991 and 2001 that addressed conversion of mild cognitive impairment to dementia. Overall the rate of conversion was 10% but with large differences between studies. The single biggest variable accounting for between study heterogeneity was source of subjects, with self-selected clinic attenders having the highest conversion rate. The most important factor accounting for heterogeneity within studies was cognitive testing, with poor performance predicting conversion with a high degree of accuracy. CONCLUSIONS: These data strongly support the notion that subjective and objective evidence of cognitive decline is not normal and predicts conversion to dementia. The more stringent the measures of both variables the better the prediction of conversion. Mild cognitive impairment, appropriately diagnosed, is a good measure with which to select subjects for disease modification studies.     

Protective effects of pharmacological therapies in animal models of multiple sclerosis: a review of studies 2014–2019

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.     

Brain functional alterations in Type 2 Diabetes – A systematic review of fMRI studies

Type 2 Diabetes (T2DM) is emerging as a major global health issue. T2DM can adversely affect cognition and increase dementia risk. This systematic review aimed to examine the functional brain changes that may underlie cognitive dysfunction in adults with T2DM. Studies were restricted to those which used functional magnetic resonance imaging (fMRI). Nineteen independent studies were identified, mostly comprised of middle aged or older adults. Resting-state studies demonstrated that compared to controls, connectivity of the Default Mode Network (DMN) was reduced and the majority of task-based studies identified reduced activation in T2DM patients in regions relevant to task performance. Abnormalities of low frequency spontaneous brain activity were observed, particularly in visual regions. As most studies demonstrated that alterations in fMRI were related to poorer neuropsychological task performance, these results indicate that functional brain abnormalities in T2DM have consequences for cognition.     

Can the emotional connotation of concepts modulate the lexico-semantic deficits in Alzheimer's disease?

Semantic memory impairments are a common symptom of Alzheimer's disease (AD) and may occur at a relatively early stage. These disturbances can be evidenced by a hyperpriming effect (greater semantic priming in AD patients than in controls). Up till now, very few studies of semantic memory have included emotionally charged concepts. Our aim was therefore to study the semantic processing of such concepts, as opposed to neutral ones, in early AD. Given that emotional processes are relatively preserved at the beginning of the disease compared with other cognitive functions, we expected that an emotional connotation would influence the spreading activation of words and affect some of the impairments in semantic processing. We administered a semantic priming task (lexical decision task) implicitly assessing semantic memory to 26 patients with AD and 26 normal controls. Primes and targets either had a semantic relationship (e.g. tiger-lion), a semantic and emotional (positive or negative) relationship (e.g. slap-smack) or no relationship at all (e.g. chair-horse), or else belonged to a word-nonword condition (e.g. window-inuly). Compared with controls, the patients showed pathological hyperpriming effects in all conditions, especially in the emotional conditions. Hyperpriming implies a deterioration in specific attributes, as it is difficult to tell two concepts apart once their distinctive attributes have been lost. These results suggest that emotional concepts, like neutral ones, lose some of their distinctive attributes in early AD, and as the emotional processes are preserved, there is greater similarity between close emotional concepts than between close neutral concepts.     

Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

1 Introduction The ability to modify synaptic strength in an activity- dependent manner, either as long-term depression (LTD) or as long-term potentiation (LTP) is a fundamental feature of most central nervous system synapses. The properties of different forms of LTP in the rodent hippocampus have been exceedingly well studied. A less well studied but par- ticularly intriguing finding is that the capacity of many syn- apses for plastic changes itself is subject to modulation of subsequent …     

Can common strengths be identified in autistic young people? A systematic review and meta-analysis

Background and methodThe purpose of this study was to systematically review the empirical literature on common strengths of autistic young people relative to their typically developing peers.ResultsForty-eight articles met inclusion criteria and were included. Of these, sixteen studies reported sufficient data for inclusion in a series of 13 meta-analyses. Only a small number of mean effect sizes were significant, with possible common strengths including auditory processing strengths (Hedges’ g = 0.54–1.22) and metaphor generation (Hedges’ g = 0.64).ConclusionsThis review highlights the need for a systematic approach to identifying strengths shared by autistic young people that could inform intervention approaches, and are important to autistic young people and their families.     

Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review

The relationship between clinical symptoms and neurocognitive impairment has been a growing interest in the field of schizophrenia research. We review the empirical evidence for whether some schizophrenia symptoms can be viewed as expressions of disordered executive functioning. A specific focus of our review is Frith's (1992) neurocognitive theory of negative symptoms, and whether this theory is supported by studies of executive functioning in schizophrenia. The current trend towards viewing executive functioning in terms of fractionable cognitive processes is discussed. Difficulties with traditional clinical measures (e.g. the Wisconsin Card Sorting Test; WCST) in separating these processes are highlighted. Neurocognitive studies of schizophrenia are then reviewed in terms of this fractionated view of executive processes. We conclude that a more specific approach to executive functioning deficits in schizophrenia using more selective measures is needed before stronger conclusions can be drawn about their relationship to clinical symptoms.     

Counter striking psychosis: Commercial video games as potential treatment in schizophrenia? A systematic review of neuroimaging studies

Schizophrenia is a severe, chronic, and strongly disabling neuropsychiatric disorder, characterized by cognitive decline, positive and negative symptoms. Positive symptoms respond well to antipsychotic medication and psycho-social interventions, in contrast to negative symptoms and neurocognitive impairments. Cognitive deficits have been linked to a poorer outcome and hence specific cognitive remediation therapies have been proposed. Their effectiveness is nowadays approved and neurobiological correlates have been reconfirmed by brain imaging studies. Interestingly, recent MRI work showed that commercial video games modified similar brain areas as these specialized training programs. If gray matter increases and functional brain modulations would translate in better cognitive and every day functioning, commercial video game training could be an enjoyable and economically interesting treatment option for patients with neuropsychiatric disorders. This systematic review summarizes advances in the area with emphasis on imaging studies dealing with brain changes upon video game training and contrasts them to conventional cognitive remediation. Moreover, we discuss potential challenges therapeutic video game development and research would have to face in future treatment of schizophrenia.     

Is 18F-FDG-PET suitable to predict clinical response to the treatment of geriatric depression? A systematic review of PET studies

Background: Geriatric depression is one of the most common psychiatric disorders in later life. It differs from earlier depression in its presentation, etiology, risk factors, protective factors and outcome. Positron emission tomography (PET) can be used to detect changes in neural circuitry in neuropsychiatric disorders, and several authors have assessed its role in the diagnosis and follow-up of patients with geriatric depression. We reviewed the current evidence on the use of fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) in geriatric depressed patients to find predictors of treatment response.

Methods: We searched PubMed/MEDLINE, Scopus, Embase, Cochrane Library, CINAHL and the PsycINFO databases to find relevant peer-reviewed articles on PET in geriatric depression using the search terms (‘PET’ or ‘positron emission tomography’) and (‘mood’ or ‘affective disorder’ or ‘affective disorders’ or ‘depression’ or ‘dysthymia’ or ‘seasonal affective disorder’).

Results: Eleven articles comprising 128 patients were included. We extracted data on glucose uptake of depressed patients and controls at baseline and after different types of intervention (total sleep deprivation followed by a recovery sleep and treatment with selective serotonin reuptake inhibitors).

Conclusions: ¹⁸F-FDG-PET showed significant alterations of glucose uptake in several brain areas, in particular the anterior cingulate cortex, which showed reduced metabolism after treatment, and was a predictor of treatment response.     

Alterations of the cerebral cortex in sporadic small vessel disease: A systematic review of in?vivo MRI data

Cerebral small vessel diseases of the brain are a major determinant of cognitive impairment in the elderly. In small vessel diseases, the most easily identifiable lesions, both at post-mortem evaluation and magnetic resonance imaging, lie in subcortical areas. However, recent results obtained post-mortem, particularly in severe cases, have highlighted the burden of cortex lesions such as microinfarcts and diffuse neuronal loss. The recent development of image post-processing methods allows now assessing in vivo multiple aspects of the cerebral cortex. This systematic review aimed to analyze in vivo magnetic resonance imaging studies evaluating cortex alterations at different stages of small vessel diseases. Studies assessing the relationships between small vessel disease magnetic resonance imaging markers obtained at the subcortical level and cortex estimates were reviewed both in community-dwelling elderly and in patients with symptomatic small vessel diseases. Thereafter, studies analyzing cortex estimates in small vessel disease patients compared with healthy subjects were evaluated. The results support that important cortex alterations develop along the course of small vessel diseases independently of concomitant neurodegenerative processes. Easy detection and quantification of cortex changes in small vessel diseases as well as understanding their underlying mechanisms are challenging tasks for better understanding cognitive decline in small vessel diseases.     

A role for the BDNF gene Val66Met polymorphism in schizophrenia? A comprehensive review

Schizophrenia is believed to arise from complex gene–environment interactions. Brain-derived neurotrophic factor (BDNF) is involved in neuronal development, differentiation and plasticity. A functional single nucleotide polymorphism that results in a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met) results in the aberrant sorting and release of mature BDNF through the activity-dependent secretion pathway. The Val66Met polymorphism has been linked to impaired neurocognitive function in healthy adults, and identified as a locus of risk for a range of neuropsychiatric disorders including schizophrenia. Here we provide a comprehensive review of the relationship between the BDNF Val66Met polymorphism and schizophrenia, integrating evidence from the fields of genetic epidemiology, clinical psychiatry, behavioral neuroscience and neuroimaging. We argue that while the Val66Met polymorphism may not be a major risk-conferring agent for the development of schizophrenia per se, there is mounting evidence that the polymorphism modulates a range of clinical features of the illness, including age of onset, symptoms, therapeutic responsiveness, neurocognitive function and brain morphology.     

The long-term effects of febrile seizures on the hippocampal neuronal plasticity – Clinical and experimental evidence

Febrile seizures are the most common seizure disorder in childhood, but their long-term effects on the developing brains especially neuronal injury and neurocognitive function remain unresolved. Recent epidemiological studies reassure that most febrile seizures do not adversely affect global intelligence and hippocampal function, such as memory. However, there are concerns regarding those children who experience febrile seizures during the first postnatal year, having prior developmental delay and pre- or peri-natal events. Magnetic resonance imaging (MRI) studies confirmed that prolonged and focal FS can occasionally produce acute hippocampal injury that evolves into atrophy. Animal studies have revealed that the exposure of hippocampal neurons to experimental febrile seizures early in life, particularly prolonged or frequently repetitive FS, or together with brain malformation, may lead to sustained dysfunction of these cells, in spite of the absence of neuronal damage. Genetic studies suggest that the relationship between febrile seizures and subsequent epilepsy and neurocognitive dysfunction is sometimes genetic, but there are complex interactions with genetic or environmental modifiers. Therefore, there is a small group of children in whom febrile seizures-induced hippocampal injury might occur. Identification of the target population for subsequent mesial temporal sclerosis is important for prevention and early intervention.     

A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time?

CONTEXT: Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. OBJECTIVE: To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. DATA SOURCES: Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. STUDY SELECTION: Population-based studies that reported primary data on deaths in people with schizophrenia. DATA EXTRACTION: Operationalized criteria were used to extract key study features and mortality data. DATA SYNTHESIS: We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86); however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). CONCLUSIONS: With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.     

Can pharmacological and psychological treatment change brain structure and function in PTSD? A systematic review

While there is evidence of clinical improvement of posttraumatic stress disorder (PTSD) with treatment, its neural underpinnings are insufficiently clear. Moreover, it is unknown whether similar neurophysiological changes occur in PTSD specifically after child abuse, given its enduring nature and the developmental vulnerability of the brain during childhood.We systematically reviewed PTSD treatment effect studies on structural and functional brain changes from PubMed, EMBASE, PsycINFO, PILOTS and the Cochrane Library. We included studies on adults with (partial) PTSD in Randomized Controlled Trials (RCT) or pre-post designs (excluding case studies) on pharmacotherapy and psychotherapy. Risk of bias was evaluated independently by two raters. Brain coordinates and effect sizes were standardized for comparability.We included 15 studies (6 RCTs, 9 pre-post), four of which were on child abuse. Results showed that pharmacotherapy improved structural abnormalities (i.e., increased hippocampus volume) in both adult-trauma and child abuse related PTSD (3 pre-post studies). Functional changes were found to distinguish between groups. Adult-trauma PTSD patients showed decreased amygdala and increased dorsolateral prefrontal activations post-treatment (4 RCTs, 5 pre-post studies). In one RCT, child abuse patients showed no changes in the amygdala, but decreased dorsolateral prefrontal, dorsal anterior cingulate and insula activation post-treatment.In conclusion, pharmacotherapy may reduce structural abnormalities in PTSD, while psychotherapy may decrease amygdala activity and increase prefrontal, dorsal anterior cingulate and hippocampus activations, that may relate to extinction learning and re-appraisal. There is some evidence for a distinct activation pattern in child abuse patients, which clearly awaits further empirical testing.     

A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson’s disease

The aim of this study was to systematically review the data published on deep brain stimulation (DBS) of the globus pallidus internus (GPi) in Parkinson’s disease (PD), and to determine its efficacy and optimal stimulation parameters. Only 22 of 4,648 articles fulfilled the inclusion and exclusion criteria of the study. The data were analysed using the Wilcoxon test. For 327 patients who underwent GPi-DBS, the preoperative baseline Unified Parkinson’s Disease Rating Scale (UPDRS) score, off-medication, mean was 52.7 (range 26.5–77.2). The postoperative UPDRS score, off-medication/on-stimulation, mean was 33.7 (range 18.7–46.2). The delta mean (the difference in mean UPDRS score between baseline and maximum follow-up) was 19.1 (range ?2.2 to 36.5) (p < 0.001). When the electrical parameters were compared against the delta UPDRS score, the analysis showed that only frequency was correlated with motor improvement (R² = 0.42, p < 0.05). Thus, GPi-DBS is a highly effective target for neuromodulation in PD. However, we found that significant clinical improvement (>50% delta UPDRS score) in PD is achieved at an amplitude of between 2.0 V and 3.5 V, a pulse-width between 75 μs and 300 μs and a frequency between 100 Hz and 190 Hz.     

Which came first,the risk of migraine or the risk of asthma? A systematic review

Objectives

We conducted this review to systematically assess the association and risk of the migraine in the patient with asthma and vice versa.