Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage.

Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia.

OBJECTIVES: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD). METHOD: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment. RESULTS: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis. CONCLUSION: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.

Agitation-associated behavioral symptoms in mild cognitive impairment and Alzheimer's dementia.

OBJECTIVES: The aim of this study is to determine the prevalence of agitation in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia (AD), and to characterize the associated behavioral symptoms. METHOD: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms was performed, including 268 MCI and 393 AD patients. Behavioral assessment was performed through Middelheim Frontality Score (MFS), Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia (CSDD). Agitated behavior was considered to be clinically relevant when one or more items of the Cohen-Mansfield Agitation Inventory (CMAI) occurred at least once a week. RESULTS: The prevalence of agitation in AD (76%) was higher than in MCI (60%; p < 0.001). Patients with agitation showed more severe frontal lobe, behavioral and depressive symptoms (MFS, Behave-AD and CSDD total scores). In agitated AD patients, all behavioral symptoms and types of agitation were more severe compared to non-agitated AD patients, but in agitated MCI patients only for diurnal rhythm disturbances. This resulted in more severe Behave-AD global scores in patients with agitation as compared to patients without agitation. Comparing MCI and AD patients, MCI patients with agitation showed more severe behavioral and depressive symptoms than AD patients without agitation. The structure of agitation in AD consisted of more aggressive and physically non-aggressive behavior than in MCI. CONCLUSION: Frontal lobe, behavioral and depressive symptoms are more severe in MCI and AD patients with clinically relevant agitation as compared to patients without agitation. However, this association is less pronounced in MCI.

Depression in mild cognitive impairment is associated with progression to Alzheimer's disease: a longitudinal study.

BACKGROUND: Behavioral and psychological signs and symptoms of dementia (BPSD) belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). OBJECTIVE: This study would like to contribute to the understanding of the prognostic role of BPSD in MCI for the progression to dementia due to Alzheimer's disease (AD). METHODS: Data were generated through an ongoing prospective longitudinal study on BPSD. Assessment was performed by means of the Middelheim Frontality Score, Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale 30-questions (GDS-30). Cox proportional hazard models were used to test the hypothesis that certain BPSD in MCI are predictors of developing AD. RESULTS: The study population consisted of 183 MCI patients at baseline. At follow-up, 74 patients were stable and 109 patients progressed to AD. The presence of significant depressive symptoms in MCI as measured by the CSDD (HR: 2.06; 95% CI: 1.23-3.44; p = 0.011) and the GDS-30 (HR: 1.77; 95% CI: 1.10-2.85; p = 0.025) were associated with progression to AD. The severity of depressive symptoms as measured by the GDS-30 was a predictor for progression too (HR: 1.06; 95% CI: 1.01-1.11; p = 0.020). Furthermore, the severity of agitated behavior, especially verbal agitation and the presence of purposeless activity, was also associated with progression, whereas diurnal rhythm disturbances were associated with no progression to AD. CONCLUSION: Depressive symptoms in MCI appear to be predictors for progression to AD.

Behavioral syndromes in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Behavioral disturbances belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). The identification of sets of symptoms is clinically interesting, as interventions targeting syndromes may be more effective than the management of individual symptoms. OBJECTIVE: This study aimed to identify, describe, measure, and compare the fundamental behavioral syndromes that underlie the observed behavioral symptoms in MCI and Alzheimer's disease (AD). METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms in MCI and dementia was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI), and Cornell Scale for Depression in Dementia (CSDD). Principal components factor analysis with Direct Oblimin rotation was carried out on the MFS score ≥5, seven cluster scores of the Behave-AD and the total scores of the CMAI and the CSDD. RESULTS: We identified three factors explaining behavior in the MCI group: a depression, a psychosis, and an agitation syndrome. Similar factors were found in AD, but the order: an agitation, a depression, and a psychosis syndrome, respectively, and the structure differed slightly. Diurnal rhythm disturbances and frontal lobe symptoms loaded with the depression syndrome in MCI and in AD they loaded with the agitation syndrome. Behavioral syndromes correlated in AD, but not in MCI, and the prevalence and severity of the behavioral syndromes were higher in AD than in MCI, except for the severity of the depression syndrome. CONCLUSION: In both MCI and AD, three similar behavioral syndromes exist, but behavior in MCI is more dominated by a depression syndrome, while behavior in AD is more subject to an agitation syndrome.

Effects of SolCos model-based individual reminiscence on older adults with mild to moderate dementia due to Alzheimer disease: a pilot study.

OBJECTIVE: To examine effects of individual thematically-based reminiscence sessions based on the SolCos model for older adults with dementia because of Alzheimer disease (AD) as a pilot study. BACKGROUND: Reminiscence activities are popular within nursing homes and generally considered to be enjoyable and helpful, however, there is a paucity of robust data demonstrating therapeutic impact. Criticisms of existing reminiscence studies include the failure to explicate the reminiscence protocol and to standardize delivery and choice of outcome measures. METHODS: In this study, 82 older adults with probable AD were recruited from psychiatric day care, inpatient, and long term care facilities. Of the study group, 41 participants were randomly selected for individual reminiscence sessions during 4 weeks performed by 1 facilitator. A control group of 41 older adults were randomly involved and had no planned reminiscence treatment of any kind in the study period. All study participants were tested pre- and postintervention period with validated assessment scales to evaluate cognition and behavior. Analyses were based on delta scores, the differences between assessment scales pre- and postintervention scores, compared between the intervention and the control group. RESULTS: A structured reminiscence protocol was developed with user involvement, and intervention group participants received 6-8 reminiscence sessions (average 7.4). The primary outcomes of Mini- Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-30) delta scores of the intervention group were significantly better than those of the control group. Participants of the intervention group with both mild and moderate AD had significantly better GDS-30 delta scores compared with the control group. Significantly better MMSE delta scores were found only in the intervention sub-group with moderate AD. Logistic regression analyses with all study participants showed an impact of reminiscence sessions on depressive symptoms measured with GDS-30. CONCLUSIONS: The pilot study results showed positive effects associated with individual thematically-based reminiscence on well-being such as depressive symptoms and cognition of participants. This is an encouraging finding after a relatively short period. Further study is necessary to confirm these results, determine sustainability and optimal delivery methods.

Brain-specific tryptophan hydroxylase, TPH2, and 5-HTTLPR are associated with frontal lobe symptoms in Alzheimer's disease.

A prospective, longitudinal study was set up to investigate possible genetic associations of behavioral and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) with two candidate genes in the serotonergic neurotransmitter pathway: serotonin transporter (SLC6A4) and brain-specific tryptophan hydroxylase (TPH2). Patients with probable AD (n = 249) were diagnosed according to NINCDS/ADRDA criteria. During follow-up, autopsy-confirmation of clinical diagnosis was obtained in 32 AD patients. Taking into account follow-up behavioral assessments by means of validated behavioral assessment scales (Middelheim Frontality Score and Behave-AD), behavioral ratings reflecting the highest scores on any behavioral item ever observed since dementia onset were calculated and applied for statistical analyses. A functional insertion/deletion polymorphism in the promoter region of SLC6A4 (5-HTTLPR) and 10 selected SNPs within TPH2 were genotyped. Single-marker allelic association analyses (TPH2, 5-HTTLPR) were performed. TPH2 allelic analyses revealed significant associations with frontal lobe symptoms, as well as with diurnal rhythm disturbances. 5-HTTLPR S allele carriers had an increased risk to display loss of insight and judgment, another frontal lobe symptom. The present prospective, longitudinal study showed that mainly frontal lobe symptoms were significantly associated with TPH2 and 5-HTTLPR polymorphisms, pointing toward a role of the serotonergic neurotransmitter system in the pathophysiology of frontal lobe symptoms in AD.

Behavioral symptoms in mild cognitive impairment as compared with Alzheimer's disease and healthy older adults.

BACKGROUND: Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aim of this study is to characterize behavior in MCI compared with Alzheimer's disease (AD) and healthy older patients. DESIGN: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI, 402 AD patients, and 108 healthy controls. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. RESULTS: Moderate-to-severe behavioral symptoms were present in 13% of MCI patients, as compared with 39% in AD patients and 3% in controls (p < 0.001). The general severity of behavioral symptoms was intermediate between controls and AD patients. The three most frequent symptoms in MCI patients were aggressiveness (49%), affective disturbance (45%), and anxiety (38%); in AD patients, the most frequent symptoms were aggressiveness (60%), activity disturbances (54%), and psychosis (40%). The prevalence and severity of frontal lobe symptoms, aggressiveness, activity disturbances, and delusions was intermediate between normal aging and AD. In addition, the severity of physically non-aggressive and verbally agitated behavior and the severity of depressive symptoms were also intermediate. CONCLUSIONS: The behavioral profile of MCI patients is characterized as an intermediate state between normal aging and AD for the prevalence and severity of certain behavioral symptoms. Follow-up is ongoing to test the hypothesis that behavioral disturbances in MCI predict progression to dementia.

Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease.

BACKGROUND: Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aims of this study are to determine the prevalence of significant depressive symptoms in MCI and Alzheimer's disease (AD) patients and to characterize the behavior associated with significant depressive symptoms in MCI and AD patients. METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cohen-Mansfield Agitation Inventory. The presence of significant depressive symptoms was defined as a Cornell Scale for Depression in Dementia total score >7. RESULTS: The prevalence of significant depressive symptoms in AD patients (25%) was higher compared with MCI patients (16%) (p = 0.005). Patients with significant depressive symptoms showed an increased severity of frontal lobe symptoms, behavioral symptoms and agitation (Middelheim Frontality Score, Behave-AD and Cohen-Mansfield Agitation Inventory total scores; p < 0.001). Also, most of the individual frontal lobe and behavioral symptoms were more prevalent and severe, resulting in higher Behave-AD global scores. Mild cognitive impairment patients with depressive symptoms showed more severe behavioral symptoms and more severe verbally agitated behavior than AD patients without depressive symptoms (p < 0.001). CONCLUSIONS: Frontal lobe and behavioral symptoms are more prevalent and severe in MCI and AD patients with significant depressive symptoms as compared with patients without depressive symptoms.