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Objective: Pain is common among nursing home residents with cognitive impairment and dementia. Pain is often underdiagnosed and undertreated, which may lead to adverse health outcomes. Nonverbal behaviors are valid indicators of pain, but the extent to which these behavioral expressions vary across levels of cognitive impairment is unknown. This study sought to examine differences in the prevalence of pain behaviors among nursing home residents with varying levels of cognitive impairment. Methods: The Minimum Data Set, version 3.0, was used to identify newly admitted nursing home residents with staff-assessed pain (2010–2016, n = 1,036,806). Staff-assessed pain behaviors included nonverbal sounds, vocal complaints, facial expressions, and protective body movements or postures over a 5-day look-back period for residents unable or unwilling to self-report pain. The Cognitive Function Scale was used to categorize residents as having no/mild, moderate, or severe cognitive impairment. Modified Poisson models provided adjusted prevalence ratios (aPR) and 95% CIs. Results: Compared to residents with no/mild cognitive impairments (any pain: 48.1%), residents with moderate cognitive impairment (any pain: 42.4%; aPR: 0.94 [95% CI 0.93–0.95]) and severe cognitive impairment (any pain: 38.4%; aPR: 0.86 [95% CI 0.85–0.88]) were less likely to have any pain behavior documented. Vocal pain behaviors were common (43.5% in residents with no/mild cognitive impairment), but less so in those with severe cognitive impairment (20.1%). Documentation of facial expressions and nonverbal pain behaviors was more frequent for residents with moderate and severe cognitive impairment than those with no/mild cognitive impairment. Conclusions: The prevalence of behaviors indicative of pain differs by level of cognitive impairment. Pain evaluation and management plays an important role in treatment and care outcomes. Future work should examine how practitioners’ perceptions of pain behaviors influence their ratings of pain intensity and treatment choices.

Background: Behavioral and psychological symptoms of dementia (BPSD) are difficult to manage and associated with poor outcome. Objectives: The aim of this study was to reach consensus on the use of antipsychotics in patients with BPSD in Spain. Methods: A qualitative, multicenter, two-round Delphi study was carried out, with the participation of specialists involved in the care of dementia patients throughout Spain. They completed a 76-item questionnaire related to the identification of BPSD, treatment with antipsychotics, follow-up of patients, barriers for the use of atypical antipsychotics, and effects of antipsychotics on quality of life. Results: A total of 162 specialists in neurology, psychiatry, and geriatrics (61% men) with a mean (SD) age of 45.9 (10) years participated in the study. Almost all participants (96.9%) strongly agreed that atypical antipsychotics are safer and better tolerated than typical antipsychotics. There was agreement on the importance to review the indication and dose of the antipsychotic drug at least every 3 months. There was consistent high rate of agreement on the beneficial impact of atypical antipsychotics on the quality of life of patients with dementia and their caregivers. A consensus was also reached on the need of detecting BPSD in patients with dementia as it decreases the quality of life of both patients and caregivers, and the need to routinely screen for dementia in elderly patients with no previous psychiatric history in the presence of suggestive symptoms of BPSD. Finally, the participants in the study agreed that administrative barriers for the prescription of atypical antipsychotics in Spain hinder the access to this drug group and favor the prescription of typical antipsychotics. Conclusions: The participants in the study agreed that atypical antipsychotics should be preferred to typical antipsychotics in the management of BPSD. Wide consensus was reached about the importance of early identification of BPSD in persons with cognitive impairment, the use and management of atypical antipsychotic drugs and their favorable impact on patients and caregiver’s quality of life.

Introduction: Behavioral variant frontotemporal dementia (bvFTD) is the most common clinical subtype of frontotemporal lobar degeneration. bvFTD is often characterized by changes in behavior and personality, frequently leading to psychiatric misdiagnoses. On the other hand, substantial clinical overlap with other neurodegenerative diseases, such as Alzheimer disease (AD), further complicates the diagnostics. Objective: Our aim was to identify the main differences in early symptoms of bvFTD and AD in the prodromal stages of the diseases. In addition, patients with bvFTD were analyzed separately according to whether they carry the C9orf72repeat expansion or not. Methods: Patient records of bvFTD (n = 75) and AD (n = 83) patients were analyzed retrospectively for memory and neuropsychiatric symptoms, sleeping disorders, and somatic complaints before the setting of the accurate diagnosis. Results: A total of 84% of bvFTD patients (n = 63) and 98.8% of AD patients (n = 82) reported subjective memory disturbances in the prodromal phases of the disease. bvFTD patients presented significantly more often with sleeping disorders, headache, inexplicable collapses, transient loss of consciousness, somatization, delusions, and hallucinations, suicidality, changes in oral behaviors, and urinary problems. In addition, poor financial judgement was frequently detected in patients with prodromal bvFTD. Aberrant sensations in the nose and throat without any physical explanation, regarded as somatizations, emerged only in bvFTD patients with the C9orf72 repeat expansion. Conclusions: Subjective reporting of impaired episodic memory is a poor indicator in differentiating bvFTD from AD. Sleeping disturbances, delusions, hallucinations, and unexplained somatic complaints in a patient with cognitive disturbances should prompt the clinicians to consider bvFTD as a possible diagnostic option behind these symptoms. The spectrum of symptoms in the prodromal stages of bvFTD may be more diverse than the latest criteria suggest.

Background: Deficits in instrumental activities of daily living (ADLs) may be more prominent in behavioral variant frontotemporal dementia (bvFTD) than in nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or semantic variant primary progressive aphasia (svPPA). It is uncertain whether frontotemporal dementia (FTD) subgroups exhibit different patterns and/or predictors of functional impairment. Methods: We examined data from participants diagnosed with bvFTD (n = 607), svPPA (n = 132), and nfvPPA (n = 155) who were included in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and assessed with the Functional Activities Questionnaire (FAQ). Stepwise multiple linear regression analyses were performed to identify associations between FAQ scores and cognitive/behavioral deficits using the NACC UDS neuropsychological testing battery and the Neuropsychiatric Inventory Questionnaire. Results: FAQ scores were higher in bvFTD than svPPA or nfvPPA. Functional deficits across FTD subtypes differed in severity, but not pattern, and were driven by executive dysfunction and behavioral symptoms. Conclusion: Executive dysfunction and behavioral symptoms underlie instrumental ADL deficits in FTD, which are most prominent in bvFTD.

Background: Accurate diagnosis of behavioral variant frontotemporal dementia (bvFTD) is important as patients' behavioral symptoms have profound implications for their families and communities. Since the diagnosis of bvFTD derives from behavioral features, accurate identification of patients can be difficult for non-specialists. Concrete rates of diagnostic accuracy among non-specialists are unavailable. Methods: To examine the accuracy of community clinicians' diagnoses of bvFTD and to identify patient characteristics leading to misdiagnosis, we reviewed the charts and referral letters of 3,578 patients who were seen at our specialized center. Referral diagnosis and reasons, manifesting symptoms, demographic data, Mini-Mental State Examination score, Clinical Dementia Rating score and Neuropsychiatric Inventory score were extracted. Results: 60% of patients assigned a single diagnosis of bvFTD by community clinicians did not have bvFTD according to specialists. Compared to specialist-confirmed bvFTD patients, false bvFTD patients were more likely to be depressed and to be non-Caucasian, showed less euphoria, apathy, disinhibition and abnormal eating behaviors, had milder disease severity and better overall cognition. bvFTD was mentioned by referring clinicians in 86% of specialist-confirmed bvFTD cases, but missed cases were called Alzheimer's, Parkinson's or Huntington's disease, or progressive aphasia. Conclusion: These results revealed a widespread lack of familiarity with core diagnostic symptoms among non-specialists and suggest that community clinicians require specialized diagnostic support before providing a definitive diagnosis of bvFTD.

The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH).We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age65 years).While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52-67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers.This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.

Aim: To conduct a prospective analysis of the neuropsychiatric symptoms (NPS) across the three categories of primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS), compare the prevalence and nature of the symptoms, and look at which symptoms could be helpful to better differentiate these PPA and PAOS categories. Methods: A total of 106 consecutive patients with a diagnosis of semantic variant (n = 13), logopenic variant (n = 37), agrammatic variant (n = 15) or PAOS (n = 41) were included in this prospective study. The NPS were measured by the Neuropsychiatric Inventory Questionnaire. Results: There were 65 patients with PPA and 41 with PAOS diagnosis. The most distinguishing features between the two groups were anxiety, apathy, aberrant motor behavior and appetite, while among the subtypes of PPA they were disinhibition and appetite changes. PPA and PAOS patients initially exhibited depression, but with increased disease duration, PAOS patients showed apathy (55.5%) while PPA patients showed disinhibition (28.6%) and aberrant motor behavior (14.3%). Conclusion: Mood symptoms like anxiety and appetite changes are more likely to be present at initial stages of PPA, whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur early in PAOS. The NPS seem to evolve with the progression of the disease in both PPA and PAOS.

Background: Structural neuroimaging studies on behavioral variant frontotemporal dementia (bvFTD) using the voxel-based morphometry (VBM) method reported not entirely consistent findings. Methods: A systematic review of VBM studies of bvFTD patients and healthy controls (HC) published in PubMed and Embase databases from 2000 to June 2011 was conducted. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely, effect size signed differential mapping, to quantitatively explore the gray matter (GM) changes between bvFTD patients and HC subjects. Results: 11 VBM studies involving 237 bvFTD patients and 297 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the anterior medial frontal cortex (BA 9), extending to other frontal areas (BA 8, 10, 46, 24, 32), and other brain areas, such as the insula cortex, as well as the subcortical striatal regions in patients with bvFTD compared with HC subjects. The findings of the present study remain largely unchanged in the entire brain jackknife sensitivity analyses. Conclusions: The present meta-analysis provides evidence of GM changes in the frontal-striatal-limbic brain areas in patients with bvFTD. Furthermore, GM atrophy in the fron-toinsular cortex and anterior cingulate cortex may be important anatomical changes for the diagnosis of patients with bvFTD.

Background: Patients with syndromes of the frontotemporal dementia spectrum are frequently unaware of their behavioral changes. Methods: Seventy patients with a clinical diagnosis of behavioral variant frontotemporal dementia (bv-FTD, n = 27), aphasic variant frontotemporal dementia (a-FTD, n = 12) and corticobasal syndrome (CBS, n = 31) participated in the study. Anosognosia for behavioral disturbances was measured as discrepancy between caregiver’s and patient’s ratings on the Frontal Systems Behavior Scale for present and premorbid behavioral symptoms. Voxel-based morphometry analysis of MRI data was performed to explore the association between anosognosia and gray matter loss. Results: Although behavioral symptoms were reported in all the groups, the comparison between present and premorbid anosognosia revealed that bv-FTD patients not only underestimated their present behavioral disturbances compared to their caregivers, but also overestimated their premorbidbehavioral disturbances. Across all groups, the degree of anosognosia for present behavioral impairment correlated with gray matter atrophy in a posterior region of the right superior temporal sulcus (adjacent to the temporoparietal junction). Conclusion: These results confirm the role of the right temporoparietal cortex in the genesis of anosognosia and suggest that, in clinical syndromes of the frontotemporal dementia spectrum, anosognosia is associated with the dysfunction of temporoparietal mechanisms of self versus others knowledge.

Background: Distinguishing between patients with frontotemporal lobar dementia (FTLD) and other dementing illnesses remains a difficult task for many clinicians. In this study, we aimed to provide further evidence for the construct validity of the frontal behavioural inventory (FBI) and assess its utility in differentiating FTLD patients from other groups using data from the Canadian Collaborative Cohort of Related Dementias (ACCORD) study. Method: Baseline scores on the FBI and neuropsychiatric inventory (NPI) were compared among several clinical groups (n = 177). Results: The FBI discriminated a higher percentage of FTLD patients (>75% correct classification) from Alzheimer’s disease and other groups compared to the NPI (54.2%). Conclusion: This study provides good evidence for convergent validity between the FBI and NPI (r = 0.72), indicating that both measures capture similar psychopathology in this nationwide cohort.

Background/Aims: Memantine has been approved by the Food and Drug Administration for the treatment of moderate-to-severe Alzheimer's disease (AD). However, the effect of memantine on patients with mild-to-moderate AD is unclear. Methods: This study is a post hoc analysis of a double-blind clinical trial. Donepezil was used as the standard control treatment. Outcomes included score changes from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a modified 20-item Activities of Daily Living Scale (ADL), the Neuropsychiatric Inventory (NPI), and the Mini-Mental State Examination (MMSE) as well as the score of the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-Plus). Results: One hundred sixty-seven AD patients with an MMSE score of 10-24 were analyzed. No significant differences in the score changes from baseline to week 24 on all outcomes or the four subscales of the ADAS-cog were observed between the two treatment groups. Donepezil resulted in an improved score for naming ability on the ADAS-cog compared to memantine (p = 0.036), whereas memantine more effectively reduced agitation as measured by the NPI compared to donepezil (p = 0.039). Conclusion: These findings support the efficacy of memantine for the treatment of mild-to-moderate AD, especially in patients with agitation.

Background: Behavioural changes are a key factor in distinguishing frontotemporal dementia (FTD) from Alzheimer’s disease (AD), however, little is known about the impact of these changes on caregivers. The aim of this study was to compare caregivers’ distress related to behavioural symptoms of AD and FTD. Methods: 47 spouse caregivers of consecutively referred patients with AD and 27 spouse caregivers of patients with FTD participated in this study. Behavioural disturbances in the patient and caregivers’ emotional reactions were measured with the Neuropsychiatric Inventory. Results: Patients with FTD had significantly higher levels of agitation, apathy, disinhibition and aberrant motor behaviour than did patients with AD. High distress scores were found for disinhibition, depression and apathy in caregivers of FTD patients whereas caregivers of AD patients reported patient apathy, depression and anxiety as being severely distressing. Higher mean distress scores were found for disinhibition in the FTD group. Furthermore, caregivers of FTD patients reported higher levels of general burden, and felt less competent than AD caregivers. Conclusions: Caregivers of FTD patients were overall more distressed by the behaviour of their partners than were the caregivers of AD patients.Findings from this study underscore the importance of differentiating between diagnostic groups and specific behavioural domains when focusing on caregiver reactions to problem behaviour.

The aim of this study was to detect behavioral subsyndromes of the 12-item Neuropsychiatric Inventory (NPI). Cross-sectional data of 199 patients with dementia living in the community were collected. Principal component analysis (with Varimax rotation) was used for factor analysis. Results showed the presence of three behavioral subsyndromes: mood/apathy, psychosis, and hyperactivity. Anxiety was regarded as a separate symptom. The subsyndrome mood/apathy was the most common, occurring in almost 80% of the patients, versus psychosis and hyperactivity, which occurred in 37 and 60% of the patients, respectively.

The aim of this study was to define the co-occurrence of behavioural symptoms and Alzheimer’s disease (AD) in relation to apolipoprotein E (APOE) genotype. Probable AD patients from the Alzheimer’s Day Clinic (n = 139) were assessed with the ‘Behavioural Pathology in Alzheimer’s Disease’ rating scale, and their APOE genotype was determined. This study demonstrated no relationship between presence of the APOE Ε4 allele and any of the behavioural symptoms assessed, including delusions, hallucinations, depression, activity disturbances, aggressiveness and anxiety. Activity disturbances, delusions, hallucinations and aggressiveness paralleled the severity of AD, increasing in frequency with the severity of the dementia. The prevalence of delusions, hallucinations, aggressiveness and depression were found to be associated with lower levels of education.

Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Bråne-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.

Clinicians fequently under-recognize delirium. Physicians and nurses can be taught to recognize delirium by focusing on each of the components of the criteria for delirium. Teachers of physicians and nurses should emphasize the ability to recognize acuteness of onset, fluctuation of course, and attention deficits. Attention deficits in the clinical setting can be recognized by digit span testing, spelling words backwards, or assessing accessibility during the clinical interview. Attention can be scored by assigning a score from 0–10, or ranking as mild, moderate or severe, the patients ability to engage in the medical interview.

The incidence of delirium, its predisposing factors, clinical profile, associated symptoms and consequences were investigated in 54 consecutive patients, 19 men and 35 women, mean age 77.1 years, admitted to an ‘ortho-geriatric unit’ with femoral neck fractures. The incidence of postoperative delirium was 15/54 (27.8%) and a logistic regression model found that dementia and a prolonged waiting time for the operation increased the risk of postoperative delirium. Delirium during the night was most common but in 5 patients the delirium was worst in the morning. Patients with delirium suffered more anxiety, depressed mood, emotionalism, delusions and hallucinations. A larger proportion of patients with delirium could not return to their previous dwelling, and a larger proportion of delirious patients were either dead, wheelchair-bound or bedridden at the 6-month follow-up (p < 0.005). The conclusion is that delirium is common and has a serious impact on the outcome after hip fracture surgery.

Delirium has been considered a syndrome of generalized dysfunction of higher cortical functions due to its breadth of symptoms and associated diffuse slowing on electroencephalogram. Advances in neuropsychiatry have revealed differences between brain regions, including the hemispheres, which may underlie the constellation of symptoms among different psychiatric disorders. For example, different neural pathways are involved in major depression and obsessive-compulsive disorder, including lateralization to one or the other hemisphere. In this article the author proposes that delirium, too, involves particular neural pathways and that lateralization to the right may be relevant. Structural and functional neuroimaging reports and recent neuropsychological studies support this lateralization. Prefrontal cortices, anterior and right thalamus, and right basilar mesial temporoparietal cortex may play a significant role in subserving delirium symptoms and may be the ‘final common pathway’ for delirium from a variety of etiologies. The final common pathway may be responsible for certain ‘core symptoms’ (disorientation, cognitive deficits, sleep-wake cycle disturbance, disorganized thinking, and language abnormalities), while other symptoms (delusions, hallucinations, illusions, and affective lability) may occur depending on the etiology causing delirium. An imbalance in the cholinergic and dopaminergic neurotransmitter systems is most commonly implicated in causing delirium, and could both account for delirium symptoms and be consistent with the neuroanatomical pathways being implicated.

DSM-IV made several revisions to the diagnostic criteria for delirium. This paper reviews the empirical data that supported these revisions. More research is needed to evaluate the usefulness of the new criteria and to further define subtypes of delirium.

In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer’s disease (AD), the Khachaturian criteria, the Tierney A3 criteria and the CERAD protocol. The sensitivity of the individual clinical diagnostic criteria, NINCDS/ADRDA and DSM-III-R, is poor (34–58%) irrespective of the pathological diagnostic criteria applied for the definite diagnosis of AD. The combination of the NINCDS/ADRDA ‘possible’ and ‘probable dementia of the Alzheimer type’ (DAT) categories has a high sensitivity (91–98%). However the combination resulted in very poor specificity (40–61%). Thus, none of the clinical diagnostic criteria is satisfactory. We found similar results when we analysed the predictive value of these clinical diagnostic criteria. The positive predictive value of NINCDS ‘probable DAT’ category and that of the DAT diagnosis by DSM-III-R is very high (89–100%). This makes the use of these categories suitable for research purposes. However, the negative predictive value of both diagnoses is poor (33–63%), making these criteria unsuitable for diagnostic purposes in clinical practice.

Background: There is a lack of clarity in the literature on the impact of antipsychotic discontinuation in dementia. Method: We conducted a systematic review and meta-analysis of published randomized controlled studies comparing the effects of antipsychotic discontinuation versus continuation in dementia. MEDLINE, EMBASE, PsycInfo, Cochrane Library and CINAHL were searched. Severity change of behavioral and psychological symptoms of dementia (BPSD) was the primary outcome. Results: Ten studies were included in the systematic review and 9 studies in the meta-analysis. The results showed that the antipsychotic discontinuation group had no statistically significant difference in BPSD severity change compared to the continuation group (n = 214, standardized mean difference: 0.19, 95% CI: -0.20 to 0.58). Secondary outcome analyses revealed that the discontinuation group included a statistically significantly higher proportion of subjects whose BPSD severity worsened (n = 366, risk ratio: 1.78, 95% CI: 1.31-2.41). Although not statistically significant, the discontinuation group appeared to have higher early study termination rates and a lower mortality during follow-up. Conclusions: This meta-analysis showed that antipsychotic discontinuation resulted in no statistically significant difference in BPSD severity change, early study terminations and mortality. However, a statistically significantly higher proportion of subjects with BPSD worsened in this group compared to the continuation group. Further studies are needed to explore the effects of antipsychotic discontinuation on BPSD.

Background/Aims: To evaluate whether dementia patients prescribed antipsychotic drugs have a higher mortality compared to unexposed patients, and to investigate whether there are differences in mortality associated with exposure to conventional versus atypical antipsychotic drugs. Methods: Retrospective population cohort study with information gathered from the Italian Health Information System. All 4,369 residents of Milan (Italy) aged 60 years or older who were newly prescribed an antidementia drug (donepezil, rivastigmine or galantamine) from January 2002 to June 2008 were included. All new users of antipsychotic drugs in this cohort were categorized according to conventional (n = 156) or atypical (n = 806) drug exposure. The mortality risks of users of conventional or atypical antipsychotics compared to nonusers were evaluated with survival analysis, considering exposure to antipsychotic drugs as a time-dependent variable. Results: Mortality was increased two- and fivefold in users of atypical and conventional antipsychotics, respectively, with respect to nonusers. Conclusions: Dementia patients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those prescribed conventional antipsychotics. At least part of the excess mortality may be due to the underlying neuropsychiatric symptoms that prompted the use of antipsychotics rather than a direct medication effect.

Background: Mild cognitive impairment (MCI) is an etiologically heterogeneous condition that is characterized by cognitive changes without impairment of activities of daily living and insufficient to represent dementia. MCI is an important risk state for dementia. Neuropsychiatric symptoms may be present in MCI. Methods: We executed a PubMed search for articles on the neuropsychiatric manifestations in MCI and reviewed their findings. Results: Behavioral abnormalities are reported in 35–75% of MCI patients with the most common being depression, apathy, anxiety and irritability. The observed variability in symptom prevalence can be explained by the different sampling methods, MCI diagnostic criteria and behavioral instruments used. There is a compelling body of evidence that MCI patients with behavioral features are more prone to develop Alzheimer’s disease (AD) than patients without these features. Conclusions: Neuropsychiatric symptoms are common features of MCI. The behavioral changes observed in MCI are similar to those of AD and may help identify the subgroup of MCI patients with prodromal AD. Large prospective longitudinal studies would greatly contribute to our understanding of the epidemiology, diagnostic and prognostic value of the neuropsychiatric features in MCI.

Background: Behavioural and psychological symptoms of dementia (BPSDs) are common. It is unclear whether associations are stronger with the absolute cognitive level or that relative to premorbid mental ability. Methods: The Neuropsychiatric Inventory (NPI) was administered to carers of patients with Alzheimer’s disease (AD). Patients underwent cognitive testing with the National Adult Reading Test (NART) to estimate premorbid IQ and 6 tests of current cognitive function. Results: 556 patients, mean age 77.3 years, had NPI scores. The total NPI score correlated significantly with most cognitive test scores, but multi-linear regression identified NART-IQ as the only significant cognitive predictor (β = –0.17, p = 0.008). Principal component analysis of the 10 NPI domains extracted 3 components corresponding to mood, frontal and psychotic factors. The NPI mood factor correlated significantly with NART-IQ (ρ = –0.14, p = 0.014) and lexical verbal fluency (ρ = –0.09, p = 0.034) only. The NPI frontal factor correlation with NART-IQ approached significance (ρ = –0.11, p = 0.053). The NPI psychotic factor correlated significantly with the Mini-Mental State Examination (ρ = –0.15, p < 0.001) and the Hopkins verbal learning test (ρ = –0.11, p = 0.013) scores. Conclusion: The relationship between BPSDs and cognition in AD is weak and largely explained by premorbid IQ. There is a stronger relationship between current cognition and psychotic symptoms.

Background: Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods: A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results: This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician’s Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug Research Computerized Cognitive Assessment System, was unchanged from baseline. Adverse events were generally mild and transient. Conclusion: Galantamine appears to be an effective and safe therapy for patients with DLB.

In Parkinsonian syndromes behavioural symptoms and dementia can be even more debilitating than motor symptoms and are an important predictor for nursing home placement and mortality. Neuropathologically, dementia seems to be primarily related to cortical changes rather than to subcortical alterations. Concerning neurotransmitter systems, the cholinergic system has been proposed to play a key role in cognitive disturbances. Based on studies with patients with Alzheimer disease, the application of cholinesterase inhibitors is vividly discussed also for dementia associated with parkinsonian syndromes. This review focuses on the specific symptoms of dementia in different parkinsonian syndromes and critically questions the effect of cholinergic treatment on cognitive functions in patients with extrapyramidal syndromes and dementia. There is evidence that medication with some cholinesterase inhibitors can enhance cognition as well as activities of daily living in dementia with Parkinson’s disease and seems to reduce behavioural disturbances in both dementia with Parkinson’s disease and dementia with Lewy bodies. The effect of treatment with cholinesterase inhibitors in progressive supranuclear palsy and corticobasal degeneration warrants carefully designed studies including a sufficient number of patients and symptom-adopted dementia scales.

Background: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. Objective: To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. Methods: The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer’s disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects’ BPSD and related caregiver distress, respectively. Results: In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. Conclusion: The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer’s disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of ‘executive functioning’). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.