El Departamento de Psiquiatría y Salud Mental del Hospital Central de la Defensa «Gómez Ulla» durante la pandemia por SARS-CoV-2 / The Department of Psychiatry and Mental Health of the Military Hospital «Gómez Ulla» during the SARS-CoV-2 pandemic

En el presente trabajo se exponen las medidas estructurales y logísticas, así como la práctica clínica planificada, para poder responder a la pandemia producida por el virus SARS-CoV-2 en el Departamento de Psiquiatría y Salud Mental del Hospital Central de la Defensa «Gómez Ulla». La planificación de la función asistencial se dividió en cinco grupos: los pacientes psiquiátricos ingresados en la Unidad de Hospitalización Breve; los pacientes con patología psiquiátrica ingresados en otros Servicios diferentes de Psiquiatría; los pacientes ambulatorios atendidos en Consultas Externas; los familiares de los pacientes ingresados por la COVID-19; el personal sanitario del Hospital Central de la Defensa «Gómez Ulla». En función de las necesidades de estos grupos asistenciales se realizó una planificación integral de la atención a los mismos. Durante el periodo 14 de marzo al 30 de mayo el 13% del grupo de profesionales del departamento de psiquiatría y salud mental, presentó síntomas moderados- graves de COVID-19; el 19% de los pacientes psiquiátricos ingresados en la unidad de hospitalización fueron COVID19 positivos, no falleciendo ninguno. El 74% de las interconsultas realizadas fueron sobre pacientes ingresados por COVID-19 que presentaron mayoritariamente cuadros confusionales de diversa intensidad o psicosis secundarias al uso de fármacos en el tratamiento activo del COVID-19. Se hicieron 4.185 llamadas a familiares, de las cuales el 14% (n=575) fueron a demanda de los propios familiares. Se hicieron más de 200 videollamadas y se mantuvo de forma telemática el 100% de las consultas externas

In this work the structural and logistical measures are exposed, as well as the planned clinical practice, to be able to respond to the pandemic caused by the virus SARS-CoV-2 in the Department of Psychiatry and Mental Health of the Central Defense Hospital «Gómez Ulla». The planning of the care function was divided into five groups: psychiatric patients admitted to the Brief Hospitalization Unit; patients with psychiatric pathology admitted to other different Psychiatric Services; outpatients treated in Outpatient Consultations; the relatives of the patients admitted by COVID-19; the health personnel of the Central Defense Hospital «Gómez Ulla». Based on the needs of these care groups, comprehensive care planning was carried out. During the period March 14 to May 30, 13% of the staff presented moderate-severe symptoms of COVID-19; 19% of the psychiatric patients admitted to the hospitalization unit were COVID19 positive, none of whom died. 74% of the inter-consultations carried out were on patients admitted for COVID-19 who presented mostly confusional symptoms of varying intensity or psychosis secondary to the use of drugs in the active treatment of COVID-19. 4.185 calls were made to family members, of which 14% (n = 575) were at the request of the family members themselves. More than 220 video calls were made and 100% of the external consultations were kept online

White matter alterations in Alzheimer's disease without concomitant pathologies.

AIMS: Most individuals with AD neuropathological changes have co-morbidities which have an impact on the integrity of the WM. This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co-morbidities. METHODS: From a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co-morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT-qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co-morbidities to analyse the expression of selected oligodendrocyte and myelin markers. RESULTS: WM demyelination was more marked in AD with co-morbidities when compared with AD cases without co-morbidities. Regarding the later, mRNA expression levels of MBP, PLP1, CNP, MAG, MAL, MOG and MOBP were preserved at stages I-II/0-A when compared with middle-aged (MA) individuals, but significantly decreased at stages III-IV/0-C. This was accompanied by reduced expression of NG2 and PDGFRA mRNA, reduced numbers of NG2-, Olig2- and HDAC2-immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V-VI/B-C. CONCLUSIONS: The present observations demonstrate that co-morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co-morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.

Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study.

OBJECTIVE: To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG). METHODS: A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16 years. Patients were divided into: (1) patients operated on based on routine outpatient EEG information, with >80% of EEGs with unilateral interictal epileptiform discharges (IEDs) ipsilateral to HS or ictal events (n = 71); and (2) patients submitted to preoperative VEEG (n = 95). To avoid the bias generated by ictal recordings, we performed a subanalysis of: (1) patients without preoperatively ictal recordings (n = 80) and (2) patients with ictal recordings in VEEG or routine outpatient EEG (n = 86). RESULTS: Groups were similar regarding gender, age at surgery, seizure onset, preoperative seizure frequency, and duration of follow-up. Overall, 136/166 (81.92%) were classified as Engel I seizure outcome, with no difference between groups; 76.84% and 88.73% of patients with and without VEEG, respectively, had Engel I postoperative seizure outcome (P = .77). The time lag until surgery was shorter in the group without VEEG (80 vs 38 months; P = .01). Considering ictal recordings, 76.74% of patients with seizures recorded and 87.50% without ictal recordings had Engel I outcome (P = .11). SIGNIFICANCE: We performed the first prospective study in a tertiary epilepsy center comparing surgical outcomes in unilateral MTLE-HS patients investigated preoperatively with and without VEEG. Based on the surgical outcome, VEEG is not imperative in patients with unilateral MTLE-HS who have compatible semiology and clearly ipsilateralized IEDs evaluated by a multidisciplinary and experienced epilepsy group.

Sedentary behavior and compensatory mechanisms in response to different doses of exercise-a randomized controlled trial in overweight and obese adults.

BACKGROUND/OBJECTIVES: To examine compensatory changes in sedentary behavior (SB) and light-intensity physical activities (LIPA) in response to a 22-week exercise training program in overweight/obese adults; and to determine if different forms of exercise training and physical activity recommendations interact with these compensatory changes. SUBJECTS/METHODS: Eighty-nine overweight and obese individuals (body mass index (BMI): 25-34.9 kg/m2, 48% males), aged 18-50 years, were randomized into four intervention groups (strength, endurance, combined strength + endurance and physical activity recommendations) with a 25-30% caloric restriction of total daily energy expenditure for 22 weeks. Energy expenditure was measured by accelerometry before, during and after the program. RESULTS: LIPA increased significantly (P<0.001) after three months and at the end of intervention compared to baseline (pre: 281±9 min; 3 months: 303±9 min; post: 312±8 min). SB percentage decreased by 5.3 at the end of the intervention (P=0.002). No interactions were observed between groups or sexes. Significant correlations were found between SB and body weight, fat mass, android fat mass and lean body mass before and after the intervention (P<0.05). LIPA was also significantly correlated with all these body composition variables in the pre-intervention, but only correlated with body weight at the end of intervention. CONCLUSIONS: There were no compensatory changes after a combined exercise and diet program; where minutes in LIPA increased and %SB decreased after the program, without differences among exercise modes. Greater physical activity levels can contribute to a better percentage and distribution of body tissues.

Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology.

AIMS: The present study analyses molecular characteristics of the locus coeruleus (LC) and projections to the amygdala and hippocampus at asymptomatic early and middle Braak stages of neurofibrillary tangle (NFT) pathology. METHODS: Immunohistochemistry, whole-transcriptome arrays and RT-qPCR in LC and western blotting in hippocampus and amygdala in a cohort of asymptomatic individuals at stages I-IV of NFT pathology were used. RESULTS: NFTs in the LC increased in parallel with colocalized expression of tau kinases, increased neuroketal adducts and decreased superoxide dismutase 1 in neurons with hyperphosphorylated tau and decreased voltage-dependent anion channel in neurons containing truncated tau were found. These were accompanied by increased microglia and AIF1, CD68, PTGS2, IL1ß, IL6 and TNF-α gene expression. Whole-transcriptome arrays revealed upregulation of genes coding for proteins associated with heat shock protein binding and genes associated with ATP metabolism and downregulation of genes coding for DNA-binding proteins and members of the small nucleolar RNAs family, at stage IV when compared with stage I. Tyrosine hydroxylase (TH) immunoreactivity was preserved in neurons of the LC, but decreased TH and increased α2A adrenergic receptor protein levels were found in the hippocampus and the amygdala. CONCLUSIONS: Complex alteration of several metabolic pathways occurs in the LC accompanying NFT formation at early and middle asymptomatic stages of NFT pathology. Dopaminergic/noradrenergic denervation and increased expression of α2A adrenergic receptor in the hippocampus and amygdala occur at first stage of NFT pathology, suggesting compensatory activation in the face of decreased adrenergic input occurring before clinical evidence of cognitive impairment and depression.

MRZH reaction increases sensitivity for intrathecal IgG synthesis in IgG Oligoclonal band negative Multiple Sclerosis patients.

Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.

The midpoint between ventilatory thresholds approaches maximal lactate steady state intensity in amateur cyclists.

The aim was to determine whether the midpoint between ventilatory thresholds (MPVT) corresponds to maximal lactate steady state (MLSS). Twelve amateur cyclists (21.0 ± 2.6 years old; 72.2 ± 9.0 kg; 179.8 ± 7.5 cm) performed an incremental test (25 W·min-1) until exhaustion and several constant load tests of 30 minutes to determine MLSS, on different occasions. Using MLSS determination as the reference method, the agreement with five other parameters (MPVT; first and second ventilatory thresholds: VT1 and VT2; respiratory exchange ratio equal to 1: RER = 1.00; and Maximum) was analysed by the Bland-Altman method. The difference between workload at MLSS and VT1, VT2, RER=1.00 and Maximum was 31.1 ± 20.0, -86.0 ± 18.3, -63.6 ± 26.3 and -192.3 ± 48.6 W, respectively. MLSS was underestimated from VT1 and overestimated from VT2, RER = 1.00 and Maximum. The smallest difference (-27.5 ± 15.1 W) between workload at MLSS and MPVT was in better agreement than other analysed parameters of intensity in cycling. The main finding is that MPVT approached the workload at MLSS in amateur cyclists, and can be used to estimate maximal steady state.

Cortical correlates of affective syndrome in dementia due to Alzheimer's disease.

Neuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy's patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease / Correlatos corticais da síndrome afetiva na demência da doença de Alzheimer

Neuropsychiatric symptoms in Alzheimer’s disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy’s patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices. .

Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submetidos à RNM. Consideramos quatro síndromes: afetiva, apatia, hiperatividade e psicose. Correlações entre imagens estruturais e os scores foram feitas pelo Freesurfer. Os resultados foram significantes com um valor de p < 0,05, corrigido para múltiplas comparações. Resultados Pacientes exibiram atrofia nos córtices entorrinais, giros temporal médio e inferior esquerdos, e precuneo bilateralmente. Houve correlação entre síndrome afetiva e espessura cortical em estruturais frontais direitas, ínsula e polo temporal. Conclusão Medidas de espessura cortical revelaram atrofia na DA. Sintomas de depressão e ansiedade foram associados à atrofia dos córtices frontal direito, temporal e ínsula. .

Amyloid and tau pathology of familial Alzheimer's disease APP/PS1 mouse model in a senescence phenotype background (SAMP8).

The amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern at early ages, whereas senescence-accelerated mouse prone 8 (SAMP8) has a remarkable early senescence phenotype with pathological similarities to AD. The aim of this study was the investigation and characterization of cognitive and neuropathological AD markers in a novel mouse model that combines the characteristics of the APP/PS1 transgenic mouse model with a senescence-accelerated background of SAMP8 mice. Initially, significant differences were found regarding amyloid plaque formation and cognitive abnormalities. Bearing these facts in mind, we determined a general characterization of the main AD brain molecular markers, such as alterations in amyloid pathway, neuroinflammation, and hyperphosphorylation of tau in these mice along their lifetimes. Results from this analysis revealed that APP/PS1 in SAMP8 background mice showed alterations in the pathways studied in comparison with SAMP8 and APP/PS1, demonstrating that a senescence-accelerated background exacerbated the amyloid pathology and maintained the cognitive dysfunction present in APP/PS1 mice. Changes in tau pathology, including the activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 ß (GSK3ß), differs, but not in a parallel manner, with amyloid disturbances.

Reliability of infrared thermography in skin temperature evaluation of wheelchair users.

STUDY DESIGN: Test-retest reliability analysis segmented by body parts. OBJECTIVES: To examine the reliability of infrared thermography (IRT) in wheelchair users (WCUs), as a noninvasive and risk-free technique to detect the natural thermal radiation emitted by human skin and to allow subsequent interpretations of temperature distributions. SETTING: Research Center on Physical Disability of Valladolid, ASPAYM Castilla y León Foundation, Spain. METHODS: Twenty-four manual WCUs (22 men, 2 women) participated in this study. Skin temperature (Tsk) of 16 and 20 areas of the front and rear upper body, respectively, were measured using an infrared camera. Two thermographic images were recorded in each session during two days separated by 24 h. Results were analyzed using descriptive statistics, intraclass correlation coefficients, coefficients of variation and side-to-side skin temperature differences (δTsk). RESULTS: The intraclass correlation coefficient produced values ranging from 15 to 95 for the various regions of interest. The coefficient of variation ranged between 1.05-6.18%. The mean Tsk of the front upper body was 31.92 °C, and that of the rear upper body was 31.77 °C. The total δTsk was 0.09±0.44°C, r=0.583. CONCLUSION: The reliability of IRT varies depending on the analyzed areas. IRT is a noninvasive and noncontact technique that allows measuring the temperature of the skin, with which to advance in WCU research.

Pattern changes of EEG oscillations and BOLD signals associated with temporal lobe epilepsy as revealed by a working memory task.

BACKGROUND: It is known that the abnormal neural activity in epilepsy may be associated to the reorganization of neural circuits and brain plasticity in various ways. On that basis, we hypothesized that changes in neuronal circuitry due to epilepsy could lead to measurable variations in patterns of both EEG and BOLD signals in patients performing some cognitive task as compared to what would be obtained in normal condition. Thus, the aim of this study was to compare the cerebral areas involved in EEG oscillations versus fMRI signal patterns during a working memory (WM) task in normal controls and patients with refractory mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). The study included six patients with left MTLE-HS (left-HS group) and seven normal controls (control group) matched to the patients by age and educational level, both groups undergoing a blocked design paradigm based on Sternberg test during separated EEG and fMRI sessions. This test consisted of encoding and maintenance of a variable number of consonant letters on WM. RESULTS: EEG analysis for the encoding period revealed the presence of theta and alpha oscillations in the frontal and parietal areas, respectively. Likewise, fMRI showed the co-occurrence of positive and negative BOLD signals in both brain regions. As for the maintenance period, whereas EEG analysis revealed disappearance of theta oscillation, fMRI showed decrease of positive BOLD in frontal area and increase of negative BOLD in the posterior part of the brain. CONCLUSIONS: Generally speaking, these patterns of electrophysiological and hemodynamic signals were observed for both control and left-HS groups. However, the data also revealed remarkable differences between these groups that are consistent with the hypothesis of reorganization of brain circuitry associated with epilepsy.

Heart rate recovery in elite Spanish male athletes.

AIM: During postexercise recovery, heart rate (HR) initially falls rapidly, followed by a period of slower decrease, until resting values are reached. The aim of the present work was to examine the differences in the recovery heart rate (RHR) between athletes engaged in static and dynamic sports. METHODS: The study subjects were 294 federated sportsmen competing at the national and international level in sports classified using the criteria of Mitchell et al. as either prevalently static (N.=89) or prevalently dynamic (N.=205). Within the dynamic group, the subjects who practised the most dynamic sports were assigned to further subgroups: triathlon (N.=20), long distance running (N.=58), cycling (N.=28) and swimming (N.=12). All athletes were subjected to a maximum exertion stress test and their HR recorded at 1, 2, 3 and 4 min (RHR1,2,3,4) into the HR recovery period. The following indices of recovery (IR) were then calculated: IR1=(HRpeak-RHR1,2,3,4)/(HRmax-HRrest)*100, IR2=(HRpeak-RHR1,2,3,4)/(HRmax/HRpeak), and IR3=HRpeak-RHR1,2,3,4. The differences in the RHR and IR for the static and dynamic groups were examined using two way ANOVA. RESULTS: The RHR at minutes 2 (138.7±15.2 vs. 134.8±14.4 beats·min⁻¹) and 3 (128.5±15.2 vs. 123.3±14.4 beats·min⁻¹) were significantly higher for the static group (Group S) than the dynamic group (Group D), respectively. Significant differences were seen between Group D and S with respect to IR1 at minutes 1 (26.4±8.7 vs. 24.8±8.4%), 2 (43.8±8.1 vs. 41.5±7.8%), 3 (52.1±8.3 vs. 49.1±8%) and 4 (56.8±8.6 vs. 55.4±7.4%) of recovery. For IR2, significant differences were seen between the same groups at minutes 2 (59.7±12.5 vs. 55.9±10.8 beats·min⁻¹) and 3 (71.0±13.5 vs. 66.1±11.4 beats·min⁻¹) of recovery. Finally, for IR3, the only significant difference between Group D and S was recorded at minute 3 of recovery (72.2±12.5 vs. 66.2±11.5 beats·min⁻¹). CONCLUSION: This work provides information on RHR of a large population of elite Spanish athletes, and shows marked differences in the way that HR recovers in dynamic and static sports.

Default mode, executive function, and language functional connectivity networks are compromised in mild Alzheimer's disease.

Alzheimer's disease (AD) is characterized by mental and cognitive problems, particularly with memory, language, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dysfunctions in functional connectivity networks (FCNs), especially in the memory related default mode network (DMN). However, little is known about the integrity and clinical significance of FNCs that process other cognitive functions than memory. We evaluated 22 patients with mild AD and 26 healthy controls through a resting state functional MRI scan. We aimed to identify different FCNs: the DMN, language, EF, and VS. Seed-based functional connectivity was calculated by placing a seed in the DMN (posterior cingulate cortex), language (Broca's and Wernicke's areas), EF (right and left dorsolateral prefrontal cortex), and VS networks (right and left associative visual cortex). We also performed regression analyses between individual connectivity maps for the different FCNs and the scores on cognitive tests. We found areas with significant decreases in functional connectivity in patients with mild AD in the DMN and Wernicke's area compared with controls. Increased connectivity in patients was observed in the EF network. Regarding multiple linear regression analyses, a significant correlation was only observed between the connectivity of the DMN and episodic memory (delayed recall) scores. In conclusion, functional connectivity alterations in mild AD are not restricted to the DMN. Other FCNs related to language and EF may be altered. However, we only found significant correlations between cognition and functional connectivity in the DMN and episodic memory performance.

Structural brain abnormalities are related to retinal nerve fiber layer thinning and disease duration in neuromyelitis optica spectrum disorders.

BACKGROUND: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. OBJECTIVE: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. METHODS: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. RESULTS: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. CONCLUSIONS: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network.

Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or "resting-state" analysis, may help to clarify this issue. Using such approaches, alterations in the default-mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting-state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default-mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy.