The objective of this critical review of the literature was to reveal the neural circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients through the association of these symptoms with neuroimaging findings. The search for articles was performed on PUBMED from January 2000 to May 2013, using the key words: Dementia AND BPSD; Dementia AND Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were reviewed and important contributions, especially regarding the psychopathological concepts discussed, were also considered even if not included in this time period. The available evidence suggests the three most relevant neurobiological models for neuropsychiatric symptoms in Alzheimer's disease are the frontal-subcortical circuits, the cortico-cortical networks, and the monoaminergic system. We discussed the association of the individual symptoms or syndromes with these models.

New research on assessing neuropsychiatric manifestations of Alzheimer´s Disease (AD) involves grouping neuropsychiatric symptoms into syndromes. Yet this approach is limited by high inter-subject variability in neuropsychiatric symptoms and a relatively low degree of concordance across studies attempting to cluster neuropsychiatric symptoms into syndromes. An alternative strategy that involves dichotomizing AD subjects into those with few versus multiple neuropsychiatric symptoms is both consonant with real-world clinical practice and can contribute to understanding neurobiological underpinnings of neuropsychiatric symptoms in AD patients. The aim of this study was to address whether the number of neuropsychiatric symptoms (i.e., presence of few [≤2] versus multiple [≥3] symptoms) in AD would be associated with degree of significant gray matter (GM) volume loss. Of particular interest was volume loss in brain regions involved in memory, emotional processing and salience brain networks, including the prefrontal, lateral temporal and parietal cortices, anterior cingulate gyrus, temporo-limbic structures and insula. We recruited 19 AD patients and 13 healthy controls, which underwent an MRI and neuropsychiatric assessment. Regional brain volumes were determined using voxel-based morphometry and other advanced imaging processing methods. Our results indicated the presence of different patterns of GM atrophy in the two AD subgroups relative to healthy controls. AD patients with multiple neuropsychiatric manifestations showed more evident GM atrophy in the left superior temporal gyrus and insula as compared with healthy controls. In contrast, AD subjects with few neuropsychiatric symptoms displayed more GM atrophy in prefrontal regions, as well as in the dorsal anterior cingulate ad post-central gyri, as compared with healthy controls. Our findings suggest that the presence of multiple neuropsychiatric symptoms is more related to the degree of atrophy in specific brain networks rather than dependent on the global severity of widespread neurodegenerative brain changes.

-Objective:To present socio-demographic characteristics, mean scores of tests and scales applied to patients with dementia and discuss the relationship between test scores, clinical diagnoses and the severity of dementia. Method: Patients (n=113) were diagnosed according to the DSM-IV criteria, and the diagnostic work-up included physical and neurological examination, auxiliary exams, cognitive and functional tests, and the evaluation of neuropsychiatric symptoms. Results: Mean age was 74.0 years. Alzheimer's disease (AD) was diagnosed in 62.8% of the patients, AD and vascular dementia in 8.8%, other dementias in 14.2%, and mild cognitive impairment in 2.7%. At least one neuropsychiatric symptom was diagnosed in 96.9% of the sample. There were significant differences on cognitive and functional performance between the groups classified according to dementia severity. Conclusion: Neuropsychiatric symptoms were quite common in patients with dementia, being more frequent as severity increased, and those symptoms were associated with functional impairment in the patients.KEY WORDS: dementia, Alzheimer's disease, vascular dementia, neuropsychiatric symptoms, activities of daily living. Perfil dos pacientes atendidos no ambulatório de demência de um hospital universitárioResumo -Objetivo: Apresentar características demográficas, escores médios de testes e escalas aplicadas aos pacientes com demência e discutir a relação dos escores dos testes com os diagnósticos clínicos e a gravidade da demência. Método: Pacientes (n=113) foram diagnosticados segundo os critérios para demência do DSM-IV, avaliados com história clínica, exame físico, exames complementares e aplicação de testes cognitivos, funcionais e neuropsiquiátricos. Resultados: A idade média foi 74,0 anos. A doença de Alzheimer (DA) foi diagnosticada em 62,8% dos casos, DA e demência vascular em 8,8%, outras demências em 14,2%, e comprometimento cognitivo leve em 2,7%, Ao menos um sintoma neuropsiquiátrico foi diagnosticado em 96,9% da amostra. Houve diferenças significativas nos escores dos testes cognitivos e escalas funcionais entre os grupos classificados segundo a gravidade de demência. Conclusão: Sintomas neuropsiquiátricos são muito comuns, mais freqüentes em casos graves, e estes sintomas estão associados ao comprometimento funcional nos pacientes com demência. PALAVRAS-CHAVE: demência, doença de Alzheimer, demência vascular, sintomas neuropsiquiátricos, atividades de vida diária.

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Background Previous research showed that mnemonic strategy training (MST) improves cognitive performance in people with MCI, and has been associated with increased brain activation consonant with the cognitive processes engaged by the training, such as, semantic memory, decision‐making, cognitive control, face processing and social cognition. Despite the growing body of literature on MST in MCI, we are not aware of any randomized controlled study that have examined the effect of MST on resting‐state functional connectivity (FC). Therefore, the aim of the present study was to investigate the effect of MST, focused on face‐name associations, on resting‐state FC in older adults with MCI. Method Twenty‐six amnestic MCI participants were randomized to one of two interventions: MST (N=14) or an Education Program (EP) (N=12). Both interventions were face‐to‐face, and occurred twice a week over two consecutive weeks (i.e., four sessions). Open‐eyes resting‐state functional magnetic resonance imaging (fMRI) was collected at pre‐ and post‐intervention. Nine regions of interest (ROIs) were selected a priori, based on areas that showed activation changes in a face‐name fMRI paradigm after MST (considering the contrast post>pre within the MST group, and in the comparison MST > EP). Changes in FC (post > pre, and pre > post) were examined through ROI‐to‐ROI analysis in the contrasts MST > EP and EP > MST. Analyses were conducted with CONN toolbox 17.f, and significant results were corrected for multiple comparison using false discovery rate (FDR). Result At post‐intervention, the MST group showed increased FC relative to the EP. Specifically, there was FC increase between the right inferior frontal gyrus (pars triangularis) and three ROIs in the left hemisphere: fusiform gyrus, temporal pole and orbitofrontal cortex. Within group analysis showed that FC increased after intervention only in the MST group, whereas the EP group showed decreased FC. Conclusion Our findings indicate that MST enhance FC in functionally relevant regions for the training; effects that support a general change in the innate connectivity that are not limited to a task‐specific condition. Our results extent the knowledge on the underlying mechanisms of MST, and may provide neurophysiological evidence of transfer.

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