The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease

BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. OBJECTIVE: To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n = 55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. RESULTS: At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment.     

Independence of changes in behavior from cognition and function in community-dwelling persons with Alzheimer's disease: a factor analytic approach

The authors' main objective was to investigate the relationship between changes in psychopathological, cognitive and activity of daily living (ADL) instrument scores over 12 months in community-dwelling persons with Alzheimer's disease (AD). A secondary objective was to evaluate the validity of dividing the Clinical Dementia Rating (CDR), a global dementia staging instrument into cognitive and functional subscores. Changes in measures of psychopathology, cognition and function between the baseline and 12-month visits were entered into these post hoc analyses of data from a one-year clinical trial to evaluate behavioral, cognitive and functional assessment instruments for use in clinical trials with AD patients. Exploratory factor analysis was used to determine whether there was independence between changes in any of these three domains of interest for this disease population; participants were a cohort of 187 well-characterized, community-dwelling persons with AD. One-year change in the behavioral symptoms of this cohort of persons with AD was statistically independent from changes in scores on cognitive and functional measures. Some evidence of independence of 12 month changes in cognitive and functional measures was found. Cognitive and functional subscores for the CDR were supported. These findings suggest that changes in behavior and cognition in dementia may have distinct pathophysiologies.     

Behavioral differences between white matter lacunar dementia and Alzheimer's disease: a comparison on the neuropsychiatric inventory

BACKGROUND AND PURPOSE: Behavioral abnormalities account for much of the morbidity of vascular dementia (VaD) and Alzheimer's disease (AD). The goals of the study were to compare the behavioral changes in patients with VaD associated with ischemic white matter subcortical changes and lacunar infarctions (VaD-WSI) to those in patients with AD. METHODS: Thirty outpatients with VaD and multiple lacunar infarctions in the periventricular white matter and 30 AD patients, matched for age and severity of dementia, were enrolled in this prospective study. The behavioral abnormalities of these patients were assessed by interviewing their caregivers with the Neuropsychiatric Inventory. RESULTS: A similar spectrum of noncognitive behavioral changes was found in AD and WSI patients. In VaD-WSI, the severity of delusions, hallucinations, aggression, irritability, aberrant motor behavior, nighttime behavior and appetite changes was correlated with cognitive decline, whereas depression, apathy, anxiety and euphoria were unrelated to the severity of dementia. In AD, none of the behavioral changes correlated with the severity of dementia. CONCLUSION: Behavioral changes are frequent in VaD-WSI and are present regardless of the severity of the cognitive decline. It is therefore important to assess behavioral as well as cognitive changes at early stages of the illness, to ensure appropriate treatment.     

Behavioral and psychological symptoms in Taiwanese patients with Alzheimer's disease

OBJECTIVE: To investigate the prevalence of and risk factors for behavioral and psychological symptoms in Taiwanese Alzheimer's disease (AD) patients. METHOD: Consecutive AD patients from the Memory Clinic of the Taipei Veterans General Hospital were studied. Cognitive function was evaluated using the Chinese version of the Cognitive Abilities Screening Instrument. Primary caregivers were interviewed for the Clinical Dementia Rating scale, the Barthel Index, and the Alzheimer's Deficit Scale. Behavioral and psychological symptoms were assessed using the Behavioral Pathology in Alzheimer's Disease Rating Scale. RESULTS: Of the 142 participants, 73 (50.7%) had at least one delusion. The most frequent delusion was delusion of theft (N=43, 30.3%). Thirty-five patients (24.6%) experienced hallucination. Fifty-seven patients (40.1%) had activity disturbances and 39 (27.5%) had aggression. Patients were divided into two subgroups according to the presence or absence of each cluster of symptoms, namely, delusions, hallucinations, activity disturbance, aggression, diurnal rhythm change, affective symptoms, and anxiety. There was no significant correlation between age, age at onset of dementia, number of years of education, and duration of illness and each cluster of symptoms. Correlation between severity of behavioral and psychological symptoms of dementia and cognitive decline was noted. CONCLUSIONS: This study revealed a high prevalence of behavioral and psychological symptoms of dementia in Taiwanese patients with AD and suggests that these symptoms are associated with cognitive deficit.     

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p =.03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.     

Anosognosia and Alzheimer's Disease: The Role of Depressive Symptoms in Mediating Impaired Insight

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p = .03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.     

The impact of behavioral impairment of functional ability in Alzheimer's disease.

This study sought to determine the relationship between behavioral disturbance and functional status in a longitudinally studied sample of patients with Alzheimer's disease (AD). One hundred and forty-nine patients meeting NINCDS-ADRDA criteria for probable AD were followed for an average of 37.3 months, with follow-up assessments every 6 months. Subjects were seen at the Alzheimer's Disease Research Center clinics at the Mt Sinai Medical Center, New York, and the Veterans Affairs Medical Center, Bronx, New York. Measures included the Physical and Self-Maintenance Scale (PSMS) and Instrumental Activities of Daily Living Scale (IADLS) of Lawton and Brody and the cognitive and non-cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS). For each patient the assessment at which they had their most severe non-cognitive symptoms as measured by the non-cognitive part of the ADAS (ADAS-NC) was determined. ADAS-NC scores at that assessment were correlated with IADLS and PSMS scores at the same assessment and at the next assessment 6 months later. While there was some modest association of ADAS-NC scores with functional impairment using pairwise correlation coefficients, none of the correlations remained significant when the severity of cognitive impairment was controlled statistically. Findings were not significantly changed when drug status was controlled. These results suggest that behavioral disturbance, while very troubling to caregivers and patients, does not substantially worsen functional ability beyond the contribution of cognitive impairment in AD. Together with previous results indicating that non-cognitive symptoms in AD are episodic and fluctuating rather than progressive, the present data suggest that interventions for non-cognitive disturbances in AD should be viewed as ways to increase patient comfort, safety and ease of care and not as ways to improve functional autonomy. The latter can be achieved only by improving the progressive cognitive deficits of AD.     

Subnormal serum vitamin B12 and behavioural and psychological symptoms in Alzheimer's disease

The objective of this study was to examine whether patients with Alzheimer's disease (AD) with subnormal vitamin B12 levels show more frequent behavioural and psychological symptoms of dementia (BPSD) than AD patients with normal vitamin B12 levels. The design was a prospective case-control study. The study took place at a memory-clinic of a department of geriatric medicine in a teaching hospital. There were seventy-three consecutive outpatients with probable AD, including 61 patients with normal and 12 patients with subnormal (<200 pg/ml) vitamin B12. BPSD were measured using the subscales disturbed behaviour and mood of the Nurses' Observation Scale for Geriatric Patients (NOSGER), the Cornell Scale for Depression and the four criteria for personality change in dementia from the International Classification of Diseases (ICD-10). Controlling for dementia duration and degree of severity of the cognitive deficits, there were significant inverse associations between vitamin B12 status and ICD-10 irritability (p=0.045) and NOSGER subscale disturbed behaviour (p=0.015). Low vitamin B12 serum levels are associated with BPSD in AD. Vitamin B12 could play a role in the pathogenesis of behavioural changes in AD.     

Neuropsychiatric symptoms and functional status in Alzheimer's disease and vascular dementia patients

Neuropsychiatric symptoms (NPS) are increasingly recognized as common in patients with dementia, both of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). In this study, 302 demented patients, 166 with AD and 136 with VaD, were evaluated for NPS according to the Neuropsychiatric Inventory (NPI) score at the Alzheimer's Evaluation Unit of Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy. A comprehensive geriatric assessment was also performed in all demented patients. The means of NPI scores did not differ in two groups. The overall prevalence of NPS was similar in both groups of patients (69.7% vs. 69.4%). Patients with AD had higher frequency in agitation/aggression and irritability/lability than VaD patients. Logistic analysis demonstrated a significant association between severity of the cognitive impairment and depression and eating disorders in both AD and VaD patients. The association with agitation/aggression, irritability/lability, and aberrant motor activity was found in AD only, and with apathy in VaD patients only. In both AD and VaD patients, there was a significant association between the impairment in activities of daily living (ADL) and the majority of NPI domains. A significant association was also found between the impairment of the instrumental activities of daily living (IADL) and agitation/aggression, anxiety, aberrant motor activity in AD and depression, apathy, irritability/lability, sleep disturbance and eating disorders in both AD and VaD patients. In particular, a causal mediation analysis was performed to better understand whether the relationship of NPS to functional impairment was direct or mediated by severity of cognitive dysfunction, i.e., Clinical dementia rating scale (CDR) score. Only agitation/aggression was mediated by the CDR score in affecting ADL status in VaD patients (OR: 1.12, 95% CI: 1.01-1.27). The NPI-Distress scores showed a significantly higher levels of distress in caregivers of AD than VaD. There were significant differences between AD and VaD patients with NPS, and these symptoms varied according to dementia subtype and severity and induced marked disability in ADL and IADL, increasing, prevalently, the distress of the caregivers of AD patients.     

Nursing home placement is related to dementia progression: experience from a clinical trial. Alzheimer's Disease Cooperative Study

OBJECTIVES: To examine the relationship between nursing home placement (NHP) and measures of change in other well-established clinical disease assessments in a longitudinal study of patients with probable AD. BACKGROUND: NHP is a common, major milestone in the natural history of AD. NHP is a readily identified event that can be accurately dated. NHP can be used in survival analyses, which are an efficient means of determining efficacy in clinical trials. NHP usually occurs in the setting of severe AD, but in cross-sectional studies, the strength of the association with disease severity has been controversial. DESIGN/METHODS: We used data from 341 AD patients who were enrolled in a recently published clinical trial of selegiline and tocopherol. At entry, all were rated as Clinical Dementia Rating (CDR) stage 2, were community-dwelling, and had an identified caregiver. Patients were followed at 3-month intervals for 2 years. We examined the relationship between four measures of dementia severity and a measure of behavioral dysfunction and NHP. The measures included changes in CDR status, changes in activities of daily living performance, changes from baseline to last measurement in dependence level, changes from baseline to last measurement on the Blessed Dementia Rating Scale (BDRS) score, and changes from baseline to last measurement on the total score and subscales of the Behavior Rating Scale for Dementia (BRSD). Statistical models were used to assess the strength of the associations. RESULTS: At the end of the 2-year period, 33% of patients had been institutionalized. The NHP patients did not differ at baseline from the not-NHP patients in gender, age, caregiver status, duration of illness, CDR sum of boxes, BDRS, or dependence level. The NHP patients had a lower baseline Mini-Mental State Examination score and a slightly worse BRSD total score. Patients reaching CDR3 were eight times more likely to be institutionalized than those who remained at CDR2. The change scores on all four dementia severity measures were strongly associated with NHP; the change score on the BRSD and its subscales were not. On the other hand, adverse events that included a behavioral disturbance, especially agitation, were associated with NHP. CONCLUSION: These data show that NHP closely reflects dementia progression in the context of a clinical trial. Coupled with the high face validity of NHP as a milestone of severe dementia, NHP is a valid primary outcome measure for AD clinical trials.     

Category verbal fluency predicted changes in behavioral and psychological symptoms of dementia in patients with Alzheimer's disease

Aim: Alzheimer's disease (AD) is characterized by cognitive symptoms and behavioral symptoms, and their association is inconsistent. The aim of this study was to investigate the relationship between cognitive function and the changes in behavioral and psychological symptoms of dementia (BPSD) in patients with AD. Methods: A total of 101 patients with probable AD were enrolled (57 women and 44 men, mean age 77.6 ± 7.7 years). The Category Verbal Fluency Test (CVFT), the Mini‐Mental State Examination (MMSE), the Constructional Praxis Test, the Delayed Word Recall Test, the Clinical Dementia Rating Scale, and the Neuropsychiatry Inventory (NPI) were administered at baseline. The NPI was reassessed with a median follow‐up duration of 10 months (range 6–18 months). The change in the NPI scores was defined as the end‐point score of the NPI minus the initial one. The associations between the changes in NPI total score, its four subdomains (hyperactivity, psychosis, affection, and apathy), and cognitive function were examined using multivariate linear models. The results were adjusted for confounders including demographics, baseline NPI, and duration of follow up. Results: The mean MMSE was 18.6 ± 5.6, the CVFT score was 7.1 ± 3.9, and the NPI score was 10.9 ± 13.8. Regression analyses found that the CVFT score (β = ?0.32, P = 0.004) was significantly associated with the change in NPI score, but not the MMSE, the Delayed Word Recall score, or the Constructional Praxis score. The CVFT score was significantly associated with changes in the psychosis subdomain (β = ?0.34, P = 0.001), but not the other subdomains. Conclusions: Our study showed that CVFT was predictive of the changes in behavior disturbance in patients with AD, particularly in the psychosis domain.     

Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease

BACKGROUND: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results. OBJECTIVE: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD. METHODS: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor). RESULTS: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression. CONCLUSION: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.     

Risperidone in the treatment of patients with Alzheimer's disease with negative symptoms

INTRODUCTION: Negative symptoms such as diminished initiative, drive, motivation, and emotional reactivity have been described in patients with Alzheimer's disease (AD). The purpose of this study was to retrospectively analyze the efficacy and tolerability of risperidone for the treatment of clinically significant positive and negative symptoms in AD. METHODS: We reviewed the charts of 50 community-residing AD patients who had been treated in a specialized university-based dementia management clinic. Clinical data comparing baseline and 12 weeks of treatment were obtained by reviewing a series of rating scales that were recorded as part of a comprehensive behavioral assessment. RESULTS: Reviewed subjects had a mean age of 79.7 6 years and a mean of 12 +/- 3.6 years of school. Seventy percent of the subjects were female and the majority was White. The mean dose of risperidone prescribed was 1.3 +/- 0.6 mg per day (range from 0.5 mg to 3.0 mg). After 12 weeks of treatment, the severity of positive and negative symptoms was significantly reduced. Importantly, improvement in negative symptoms with the use of risperidone appeared to be independent of a positive treatment effect on positive symptoms. Risperidone had insignificant effects on both cognitive status and the emergence of extrapyramidal symptoms. CONCLUSION: This retrospective study demonstrates that risperidone appears to be efficacious in the treatment of clinically significant positive and negative symptoms in patients with AD.     

The interrelations between psychosis, behavioral disturbance, and depression in Alzheimer disease

Behavioral changes are common in Alzheimer disease (AD), and heterogeneous in their presentation. Subtle personality changes tend to occur early; these include apathy, irritability and inability to pay attention. Later agitation, aggression and disinhibited behaviors may appear. We have utilized the Columbia University Scale for Psychopathology in Alzheimer's Disease to monitor a number of behavioral symptoms in 235 patients with early probable AD. Markov analyses were used to predict the probability of developing or retaining a given symptom at 6-month follow-up. The results show that the symptoms of psychopathology in AD fluctuate with time. Agitation was both the most frequent and persistent symptom, while paranoid delusions and hallucinations were less persistent. Most behavioral disturbances, except paranoid delusions, were associated with greater cognitive impairment. There was no association between depressive features and either cognitive or functional impairment. These results have important implications for the optimal treatment of the psychopathological symptoms of AD.     

Personality changes in Alzheimer's disease

BACKGROUND: Assessment of personality changes in patients with dementia has received little systematic investigation, although caregivers report personality modifications in every phase of dementia. METHODS: A group of 52 patients with probable Alzheimer's disease (AD) vs. a group of fifteen control subjects were selected for these personality tests before and after the manifestation of dementia using an Italian version of Brooks and McKinaly's Personality Inventory (PI). RESULTS: After the onset of AD, a significant shift from positive to negative characteristics in PI was observed in 12 of 18 bipolar pairs of adjectives constituting the instrument and the total mean PI score decreased significantly (p < 0.001), indicating a substantial worsening of personality profile. In the control group however, evaluated before and after retirement, personality traits and total mean PI score did not show a significant change. The association of personality traits and total PI score with demographic, cognitive and functional characteristics of AD patients was calculated. CONCLUSION: Personality changes have been depicted to be influenced by severity of cognitive, functional and behavioural complaints rather than age, sex, education and disease duration. These first applications of the Italian version of PI confirmed that personality modifications make a consistent aspect of the phenomenology of AD although in the negative direction. Further studies are needed to understand the nature of personality changes in dementia and the utility of PI to investigate these changes.     

Lifetime symptoms of depression in Alzheimer's disease.

INTRODUCTION: Depression is common in Alzheimer's disease (AD). The symptomatology of depression in dementia may differ from depression alone. Consequently, the reports on lifetime depressive symptoms were compared in AD patients and age-matched non-demented participants. METHODS: Seventy-six AD patients, 109 elderly from the general population and their 189 siblings were examined using the Composite International Diagnostic Interview (CIDI). The presence of individual lifetime depressive symptoms was compared between 76 AD patients, 29 AD patients with comorbid depression, and different control groups using chi(2) statistics and logistic regression analysis. RESULTS: Lifetime depressive symptoms were significantly more frequent in 76 AD patients than in 109 age-matched elderly from the general population. These 76 AD patients complained more about thinking and concentration disturbances, and less about depressed mood or appetite disturbance than the 298 non-demented participants matched for the lifetime presence of major depression (MD). In agreement, the 29 patients comorbid for lifetime diagnoses of AD and MD reported less about depressed mood than the 114 age-matched elderly with MD only. Feelings of worthlessness and suicidal ideas were related to the severity of cognitive decline. CONCLUSION: AD influences the reports on lifetime depressive symptoms. This may be caused by additional neurodegeneration, by an overlap of symptoms of depression and dementia or by an altered perception of mood disturbances in AD. Further studies should investigate these alternatives.     

Apolipoprotein E genotype influences presence and severity of delusions and aggressive behavior in Alzheimer disease

AIM: We investigated differences in the prevalence and severity of 10 neuropsychiatric and behavioral symptoms according to apolipoprotein E (APOE) genotype and dementia severity in Alzheimer disease (AD). METHODS: Neuropsychiatric and behavioral symptoms of 110 AD patients were assessed using the Neuropsychatric Inventory. Dementia severity was assessed using the Mini Mental State Examination (MMSE). RESULTS: There were 27 APOE-epsilon4-negative patients, 65 heterozygous patients and 18 homozygous patients. There was a significant association between the number of APOE epsilon4 alleles and prevalence and severity of neuropsychiatric and behavioral symptoms that was mainly attributable to delusions and agitation/aggression, which were more common and severer among homozygous APOE epsilon4 carriers. In addition, the presence of hallucinations, anxiety, apathy and aberrant motor behavior increased with deteriorating MMSE score, independently of APOE epsilon4 status. CONCLUSIONS: The present study showed that the APOE epsilon4 genotype modifies neuropsychiatric and behavioral phenotype in AD. In particular, it was shown that delusions and agitation/aggression were more common and severer among homozygous APOE epsilon4 carriers than among heterozygous or APOE-epsilon4-negative patients.     

Executive dysfunction in Alzheimer disease

BACKGROUND: Executive dysfunction (EDF) is common in Alzheimer disease (AD); however, its relationship to other symptoms is difficult to assess in patients with AD. OBJECTIVES: To determine the prevalence of EDF and study its relationship to cognitive, functional, and neuropsychiatric symptoms in patients with AD. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of data from participants in the English Instruments Protocol of the Alzheimer's Disease Cooperative Study. Subjects were drawn from a sample of patients evaluated at tertiary referral centers. RESULTS: A total of 64% of AD patients were classified as having EDF. Patients with EDF performed worse on tests of cognition (P <.001), dementia severity (P <.001), and activities of daily living (P =.01) and had more frequent symptoms of psychosis (P =.03) with greater emergence during the 12-month interval (P =.03) compared with patients with normal executive function. Less than 30% of the variance in executive function performance was explained by cognitive measures. CONCLUSION: These findings support the assessment of executive function in persons with AD and the importance of frontal lobe dysfunction in AD.     

Depression in Alzheimer's disease: Phenomenological features and association with severity and progression of cognitive and functional impairment

Seventy-eight outpatients with a clinical diagnosis of dementia in Alzheimer's disease according to the ICD-10 draft research criteria were investigated with annual evaluations over a period of 2 years to study the phenomenology and association with severity and progression of cognitive and functional impairment of depression in Alzheimer's disease. As measured by the Dementia Mood Assesment Scale (DMAS), depressive symptoms occurred frequently, such as decrease in motor activity, lack of responsiveness, agitation and depressed appearance. Multiple stepwise regression demonstrated that decrease in motor activity and lack of responsiveness were the strongest contributors to an association of depressive symptoms with severity of cognitive and functional impairment. The global score of the DMAS mood subscale was not related to dementia severity. There was no relation between depressive symptoms in Alzheimer's disease and the rate of cognitive and functional decline within a 12-month and 24-month observational period. Our results suggest that depressive symptoms are frequent concomitants of dementia in Alzheimer's disease. Depressive symptoms are in part associated with a greater severity of cognitive and functional impairment in Alzheimer's disease. However, depressive symptoms, unlike other non-cognitive psychopathological symptoms, for example psychotic phenomena, are not prognostically relevant with respect to a lower or higher rate of symptom progression.     

Depression in patients with moderate Alzheimer disease: a prospective observational cohort study

Syndromes of depression are frequently concomitant with Alzheimer disease (AD), although often inaccurately diagnosed and/or treated. This prospective, multicenter, observational, cohort study assessed baseline data and 6-month disease changes in moderate AD patients (n=1249) from Spain. Baseline Cornell Scale for Depression in Dementia (CSDD) scores defined 2 cohorts (depressive ≥8 or nondepressive <8). Fewer patients had baseline Diagnostic and Statistical Manual for Mental disorders-IV depression diagnosis (38.9%) than CSDD ≥8 (55.6%). Analysis of diagnostic accuracy of the CSDD versus the Diagnostic and Statistical Manual for Mental disorders-IV criteria showed an optimal cutoff score of ≥12. However, the predefined CSDD cutoff score showed subsyndromal depressive symptomatology associated with lower functionality, worse neuropsychiatric symptomatology, increased caregiver distress, and greater 6-month functional and clinical impairments. Cognition (baseline and 6-month progression) was not significantly associated with depressive symptomatology. Depressive patients received more antidepressive and/or antipsychotic treatments, showing CSDD and Neuropsychiatric Inventory Questionnaire (severity and caregiver distress) 6-month improvements but maintaining doubled scores than nondepressive patients. In conclusion, CSDD ≥8 identified depressive symptomatology in moderate AD patients, significantly associated with excessive neuropsychiatric symptoms and functional, but not cognitive, 6-month deterioration. The health effects over patients and caregivers, alongside the finding that most patients remained depressive after 6 months, demand accurate diagnostic tools and effective treatments for depression in AD.