Neuropsychiatric Inventory Apathy Research Articles

The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial

BackgroundAlzheimer’s disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings.MethodsThe Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months.DiscussionGiven the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a treatment for apathy in AD. With a larger sample size and longer follow up, ADMET 2 is poised to confirm or refute the original ADMET findings.Trial registrationClinicalTrials.gov, NCT02346201. Registered on 26 January 2015.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease.

Background and PurposeApathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy.MethodsSixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed.ResultsAD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p<0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β=−0.25; p=0.04).ConclusionsHypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

Computerized assessment of goal-directed behavior in Parkinson’s disease

ABSTRACTIntroduction: Apathy is a syndrome characterized by a reduction in goal-directed behavior. Neurodegenerative diseases frequently exhibit apathy. However, we lack an objective measure of apathy. The Philadelphia Apathy Computerized Task (PACT) measures impairments in goal-directed behavior that contribute to apathy, including initiation, planning, and motivation. We sought to examine these mechanisms in Parkinson’s disease (PD) patients. Method: PD patients and healthy controls with a caregiver were recruited for the study. Participants were administered the PACT, a novel computerized assessment of goal-directed behavior based on reaction times, and the Starkstein Apathy Scale (AS). Care partners completed the Neuropsychiatric Inventory (NPI). Baseline demographic characteristics of PD and control participants were compared using t tests and Wilcoxon rank sum tests. Linear regressions were used to compare PD patients to controls on each of the three PACT subtasks (initiation, planning, and motivation) while controlling for motor slowing. We then compared performance on each PACT subtask between PD subjects defined as apathetic using the NPI and Starkstein Apathy Scale and controls. Results: We included 30 PD and 15 control participants in the analysis. When controlling for motor slowing, both all PD and PD apathetic subjects were significantly slower than controls on the planning task and on the initiation task. There were no significant differences between PD patients and controls on the motivation tasks. Conclusions: PD patients showed specific initiation and planning deficits compared to control participants. After using traditional scales to define apathy, PD apathetic patients still exhibited impaired initiation and planning behaviors. These results suggest that the PACT measures aspects of impaired goal-directed behavior that may contribute to apathy in PD.

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China

ABSTRACTBackground and aims: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia.Method: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI).Results: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients.Conclusion: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.

Effect of lumbo-peritoneal shunt surgery on neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus

IntroductionPatients with idiopathic normal pressure hydrocephalus (iNPH) have neuropsychiatric symptoms that could affect patients' quality of life and caregiver burden. In this study, we assessed the effect of lumbo-peritoneal (L-P) shunt surgery on neuropsychiatric symptoms and the association between neuropsychiatric symptoms and caregiver burden after L-P shunt surgery. MethodsWe recruited 22 iNPH patients who had L-P shunt surgery and who were followed up for 3months after surgery. Neuropsychiatric symptoms and caregiver burden were evaluated with the Neuropsychiatric Inventory (NPI) and Zarit Burden Interview (ZBI), respectively, before and 3months after surgery. We evaluated the changes of NPI and ZBI and the association between the changes in these 2 scores and the triad symptoms. ResultsNPI total, apathy, and depression scores significantly decreased after surgery. The improvement in NPI total, apathy, disinhibition, and irritability scores after surgery were significantly and positively associated with improvement in ZBI score after surgery. Improvement in NPI apathy score was significantly associated with improvement in Frontal Assessment Battery score after surgery. ConclusionL-P shunt surgery was effective in reducing not only the triad symptoms but also the neuropsychiatric symptoms, and the improved neuropsychiatric symptoms might decrease caregiver burden for iNPH patients.

Validation of the Lille's Apathy Rating Scale in Very Mild to Moderate Dementia

Apathy is one of the most common and disabling syndromes of dementia and presents at all stages of the disease. Comprehensive and structured methods to assess apathy in dementia are still needed. Lille's Apathy Rating Scale (LARS) has shown good psychometric properties for apathy evaluation in Parkinson disease but has not been validated in dementia. The aim of this study was to validate the LARS in a cohort of patients with very mild to moderate dementia. 101 patients with cognitive impairment (Clinical Dementia Rating ≤ 2) and 50 healthy subjects were recruited. Patient diagnoses included 43 individuals with Alzheimer disease, 41 frontotemporal dementia, and 17 primary progressive aphasia. In addition to LARS, the following assessments were administered: Clinical Dementia Rating, Interview for Deterioration in Daily Living Activities in Dementia, Functional Activities Questionnaire, Frontal Behavioral Inventory, Neuropsychiatric Inventory (NPI), and Hamilton Depression Rating Scale. Internal consistency for LARS (Cronbach's alpha) was 0.940. Test-retest intraclass correlation coefficient (ICC) was 0.940 and inter-rater ICC was 0.987. The correlation among LARS and NPI apathy scores (concurrent validity) was 0.834. Receiver operating characteristic analysis estimated an area under the curve of 0.987. The optimal cutoff point was -10. Although total LARS score was influenced by the presence of depression, this disorder was independent with respect to apathy. LARS is reliable and valid for detecting and quantifying apathy in patients with dementia, even in very early stages of the disease.

Analysis of Related Factors of Behavioral and Psychiatric Symptoms in Vascular Dementia

Objective: The aims of this study were to investigate the relationship between behavioral and psychological symptoms and cognitive disturbances, ages, educations of patients and investigate the correlations among Neuropsychiatric inventory (NPI) items in patients with vascular dementia (VaD). Methods: NPI and Mini-Mental State Examination (MMSE) were used to assess the behavioral and psychological symptoms in 120 cases with VaD and 61 cases healthy elders as control group. Results: The score about delusion, hallucination, agitation, dysphoria, apathy, irritability, aberrant motor and appetite/eating change in the NPI list were significantly increased compared with control group (P<0.05), in which the highest score in turn were dysphoria, apathy and irritability. Among the 8 items in the NPI list, delusion, apathy and aberrant motor were significantly corelated with cognitive disorder (P<0.05), and abnormal behavior was corelated with ages and educations. Besides, NPI factors analysis showed there were three behavioral sub-syndromes, such as psychosis, mood disorder and behavioral disturbance. Conclusions: Behavioral and psychological symptoms were common in VaD patients, and the frequency and severity of behavioral and psychological symptoms were corelated with cognitive disturbances, ages, and education status at different degrees.

Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial

Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses. MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale--Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6-DS baseline)) - (placebo (DS week 6-DS baseline)). In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06-1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09-1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment. These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.

Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Apathy in Dementia Methylphenidate Trial (ADMET). Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was -1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group. Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. ClinicalTrials.gov identifier: NCT01117181.

Initiation Difficulty and Apathy in Behavioral Variant Frontotemporal Degeneration (PD7.001)

Objective: To investigate initiation difficulty in apathetic patients with behavioral variant Frontotemporal Degeneration (bvFTD). Background The syndrome of apathy, defined as a reduction in self-generated or voluntary behavior, is caused in part by disruption of a frontal-striatal initiation system. Apathy is prevalent in bvFTD and is the most disturbing behavioral feature for caregivers. Previous approaches measuring apathy have depended on caregiver surveys, but are confounded by caregiver stress. Here we describe an objective, quantitative assessment of apathy. Design/Methods: We assessed patients with mild bvFTD (mean MMSE=26.42; n=12) and demographically-matched controls (NC; n=10). We surveyed apathy with Neuropsychiatric Inventory (NPI) apathy severity (FxS, worst possible score =12) and caregiver distress (worst possible score =5) scales. To quantify apathy objectively, we measured reaction time (RT) to hit a target key in response to a simple visual stimulus presented on a computer screen (24 trials). A trial began with the patient depressing a key on the computer keyboard. We examined both the RT to lift the finger from the start key in response to visual stimulus onset (initiation time), and to press a target key to complete a trial (overall time). Initiation RT was related to grey matter atrophy using voxel-based morphometry. Results: Mean NPI apathy FxS was 5.91; mean caregiver stress was 2.5. Apathy severity was correlated with caregiver distress (p=.054). Initiation RT and overall RT were significantly slower in bvFTD than NC (both p Conclusions: Patients with bvFTD have difficulty with initiation that contributes to apathy. This is related to atrophy in frontal regions important for goal-directed behavior. Apathy severity rating scales are confounded by caregiver stress and here we quantified apathy in bvFTD with an objective measure that is not confounded by proxy report. Supported by: The John A. Hartford Foundation9s Building Academic Geriatric Nursing Capacity Award Program, US Public Health Service (AG17586, AG15116, AG10124, NS53488 and NS44266) and the Wyncote Foundation. Disclosure: Dr. Massimo has nothing to disclose. Dr. Morgan has nothing to disclose. Dr. Chandrasekaren has nothing to disclose. Dr. Boller has nothing to disclose. Dr. Camp has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Grossman has nothing to disclose.

A Comparative Validation of the Abbreviated Apathy Evaluation Scale (AES-10) With the Neuropsychiatric Inventory Apathy Subscale Against Diagnostic Criteria of Apathy

To compare the Neuropsychiatric Inventory apathy subscale (NPIa) with the abbreviated Apathy Evaluation Scale (AES-10) on discriminant validity and on their performance to distinguish residents as apathetic or nonapathetic. Cross-sectional design. Nursing home. 100 residents of 4 dementia special care units (n= 58) and 3 somatic units (n= 42). Primary professional caregivers were interviewed to score the AES-10 and NPIa. The elderly care physician and the psychologist of each unit examined residents for clinical apathy using diagnostic criteria. The AES-10 and NPIa correlated moderately with each other (r(s)= 0.62, P < .0001). The AES-10 correlated weakly (r(s)= 0.27, P= .024) and the NPIa moderately (r(s)= 0.46, P= .001) with the Cornell Scale for Depression in Dementia. Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.72 (P < .01) for AES-10 and 0.67 (P < .05) for NPIa. The AES-10 produced higher sums of sensitivity and negative predictive value than the NPIa. Explorative analyses revealed that both instruments produced higher scores in dementia independently of having an apathy diagnosis, whereas AUCs were significant in nondementia (AES-10: AUC= 0.88, P < .001; NPIa: AUC= 0.77, P= .023), but not in dementia. Both the AES-10 and NPIa may be used to distinguish apathetic from nonapathetic residents in a heterogeneous sample with and without dementia, or in residents without dementia. The AES-10 may be preferable to the NPIa apathy subscale when ruling out or screening for apathy. The performance of the scales against diagnostic criteria of apathy in dementia need to be further examined.

Diagnostic criteria for apathy in clinical practice

Apathy is an important and distressing behavioural symptom in Alzheimer's disease and in various neuropsychiatric disorders. Recently, diagnostic criteria for apathy have been proposed. In groups of patients suffering from different neuropsychiatric diseases, (i) to estimate the prevalence of patients meeting the proposed diagnostic criteria; (ii) to estimate the concurrent validity of the criteria with the neuropsychiatric inventory (NPI) apathy item; (iii) to identify the most frequently met criteria or sub-criteria in each specific neuropsychiatric disease and (iv) to estimate the inter-observer reliability of the diagnostic criteria for apathy. This cross-sectional, multicentric, observational study was performed on 306 patients. Each of the participating centres had to check the presence of apathy according to the diagnostic criteria for apathy in consecutive patients belonging to the following diagnoses list: Alzheimer disease (AD), mixed dementia, mild cognitive impairment (MCI), Parkinson's disease (PD), Schizophrenia (DSM-IV) and major depressive episode. In addition to the clinical interview, the assessment included the Mini Mental Score Examination (MMSE) and the NPI. At the end of the visit, clinicians were required to check the diagnostic criteria for apathy. Using the diagnostic criteria for apathy, the frequency of apathy was of 53% in the whole population, 55% in AD, 70% in mixed dementia, 43% in MCI, 27% in PD, 53% in schizophrenia and 94% in major depressive episode. In AD, mixed dementia, MCI and PD, the NPI apathy score was significantly higher for patient fulfilling the apathy criteria. Goal-directed cognitive activity (criteria B2-Cognition) was the most frequently observed domain followed by goal-directed behaviour (criteria B1-Behaviour) and emotion (criteria B3), respectively. Inter-rater reliability was high for the overall diagnostic (κ coefficient = 0.93; p = 0.0001) and for each criteria. This study is the first one to test the diagnostic criteria for apathy in clinical practice. Results make the diagnostic criteria useful for clinical practice and research.

Neuropsychiatric Predictors of Progression from Amnestic-Mild Cognitive Impairment to Alzheimer's Disease: The Role of Depression and Apathy

The aim of the study is to evaluate whether depression or apathy in patients with amnestic-mild cognitive impairment (MCI) increases the risk of progressing to Alzheimer's disease (AD). We investigated 131 consecutive memory-clinic outpatients with newly-diagnosed amnestic-MCI (mean age 70.8, SD=6.5). Psychiatric disorders were diagnosed at baseline according to the criteria for depression and apathy in AD. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI). Follow-up examinations were conducted after six months and annually for four years. Neurologists diagnosed AD at follow-up using NINCDS-ADRDA criteria. Cox proportional hazard models with 95% confidence intervals were used to test the hypothesis that apathy or depression increases the risk of developing AD. At baseline, 36.6% amnestic-MCI patients had a diagnosis of depression and 10.7% had apathy. Patients with both amnestic-MCI and an apathy diagnosis had an almost sevenfold risk of AD progression compared to amnestic-MCI patients without apathy (HR=6.9; 2.3-20.6), after adjustment for age, gender, education, baseline global cognitive and functional status, and depression. Furthermore, the risk of developing AD increased 30% per point on the NPI apathy item (HR=1.3; 1.1-1.4). There was no increased risk of developing AD in amnestic-MCI patients with either a diagnosis or symptoms of depression. In conclusion, apathy, but not depression, predicts which patients with amnestic-MCI will progress to AD. Thus, apathy has an important impact on amnestic-MCI and should be considered a mixed cognitive/psychiatric disturbance related to ongoing AD neurodegeneration.

Apathy Associated with Alzheimer Disease: Use of Dextroamphetamine Challenge

To assess the role of the dopaminergic brain reward system (BRS) in apathy associated with Alzheimer disease (AD). BRS function was probed in 20 AD patients using dextroamphetamine (d-amph) challenge. After baseline behavioral testing, patients were given a single 10 mg dose of d-amph. The time course of the subjective response to d-amph was assessed at hourly intervals for 4 hours. Three outpatient dementia clinics associated with a university-affiliated hospital. Twenty AD patients aged 77 +/- 8 years with Neuropsychiatric Inventory (NPI) apathy scores of 3.4 +/- 3.5 and Mini-Mental State Examination scores of 20.4 +/- 5.1. Patients were classified as apathetic based on an NPI apathy subscore of > or =4. Apathy severity was assessed using the Apathy Evaluation Scale (AES). The subjective and behavioral responses to d-amph were assessed using computerized versions of the Addiction Research Centre Inventory (ARCI), Profile of Mood States and Connor's Continuous Performance Task. Repeated measures ANOVA revealed a significant interaction between the presence of apathy and the peak subjective response to d-amph on the ARCI, such that while nonapathetic AD patients were responsive to the rewarding effects of d-amph, apathetic patients were not (F(1,17) = 4.93, p = 0.04). Continuous AES scores were predicted by peak ARCI positive effects scores and baseline overall behavioral disturbances (NPI total) in a backward linear regression analysis using the entire study sample (F(2,17) = 10.00, p = 0.01, R(2) = 0.49). Apathy in AD is associated with a blunted subjective response to d-amph, which may be indicative of dysfunction in the BRS.

A Review of Rating Scales for Measuring Behavior Change Due to Frontal Systems Damage

To perform a critical review of scales designed to measure frontal behavior change. Changes in cognition due to frontal disease or damage have been well described, but noncognitive changes in behavior are often more deleterious functionally for frontal patients. The review concentrates on five behavior rating scales: the Behavior Rating Inventory of Executive Functions (BRIEF), the Dysexecutive Questionnaire (DEX), the Frontal Behavior Inventory (FBI), the Frontal Systems Behavior Scale (FrSBe), the Iowa Rating Scales of Personality Change (IRSPC), and the Neuropsychiatric Inventory (NPI). Other scales purporting to measure specific aspects of frontal functioning, but having less research support, are described briefly. The BRIEF and FrSBe have good reliability and large-scale norms. No norms are available for the other scales. The FrSBe and IRSPC have been shown to be valid in discriminating frontal from nonfrontal lesioned patients, but this has not been shown in the other scales. The FBI and NPI require trained raters, whereas the FrSBe, IRSPC, and BRIEF are administered to patients and/or family informants directly. The NPI and FBI are sensitive to certain changes in behavior attributed to frontal systems disruption but have been used primarily in dementia.

The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment.

This study was designed to establish the validity and reliability of the apathy inventory (IA), a rating scale for global assessment of apathy and separate assessment of emotional blunting, lack of initiative, and lack of interest. Information for the IA can be obtained from the patient or from a caregiver. We evaluated 115 subjects using the IA, consisting of 19 healthy elderly subjects, 24 patients with Mild Cognitive Impairment (MCI), 12 subjects with Parkinson's disease (PD) and 60 subjects with Alzheimer's disease (AD). Internal consistency, item reliability, and between-rater reliability were high. A test-retest reliability study demonstrated that caregiver responses to IA questions were stable over short intervals. A concurrent validity study showed that the IA assesses apathy as effectively as the Neuro Psychiatric Inventory apathy domain. In the caregiver-based evaluation, AD subjects had significantly higher scores than controls, both for global apathy score and for the lack of interest dimension. When the AD patients were subdivided according to diagnostic criteria for apathy, apathetic patients had significantly higher scores than non apathetic patients. With the patient-based evaluations, no differences were found among the AD, MCI and control groups. The scores in the patient-based evaluations were only higher for the PD group versus the control subjects. The results also indicated that AD patients had poor awareness of their emotional blunting and lack of initiative. The IA is a reliable method for assessing in demented and non-demented elderly subjects several dimensions of the apathetic syndrome, and also the subject's awareness of these symptoms.

Negative symptoms, depression and Alzheimer's disease.

To apply the negative symptoms (NS) concept used in schizophrenia to patients with AD, to compare the results with the frontal lobe perfusion in ethyl cysteinate dimmer (ECD) single-photon emission computed tomography (SPECT) and with the apolipoprotein E genotype. 32 patients with a diagnosis of probable AD were assessed by the Positive and Negative Symptoms Scale (PANSS-N), the Montgomery and Asberg Depression Scale (MADRS), the NeuroPsychiatric Inventory (NPI), and the Mini-Mental Status Examination (MMSE). Each patient underwent ECD SPECT and APO E genotyping. PANSS-N, MADRS, NPI, and MMSE were administered to 19 normal elderly control subjects. The mean PANSS-N score for AD patients (20.56, SD: 8, range: 7-40) was significantly higher (p < 0.001) than that of controls (7, SD: 0). MADRS scores were not significantly different (p = 0.75) between AD patients (9.03, SD: 6.14, range: 0-25) and controls (6.2, SD: 3.61, range: 1-15). The NPI apathy score (0-12) was correlated with PANSS-N (p < 0.001). Correlation between prominent frontal hypoperfusion (six cases) and NS was at the limit of significance. No relation was found between epsilon E4 and NS. This consideration is important in distinguishing between depression and AD.