Factors that predict cognitive decline in patients with subjective cognitive impairment.

BACKGROUND: Current evidence supports the concept of a preclinical phase of Alzheimer's disease (AD) where pathological and imaging changes are present in asymptomatic individuals. Subjective cognitive impairment (SCI) may represent the earliest point on the continuum of AD. A better understanding of the baseline characteristics of this group of patients that later decline in cognition will enhance our knowledge of the very early disease processes, facilitate preventive strategies, early diagnosis, timely follow-up and treatment. METHODS: An observational exploratory study which followed up 62 consecutive patients with SCI presenting to a memory clinic and compared baseline characteristics of SCI patients who declined cognitively with those who did not. Cognitive decline was defined as a progression to a diagnosis of amnestic mild cognitive impairment (aMCI) or dementia at follow-up. RESULTS: Patients were followed up for a mean of 44 months (range 12-112 months). At the time of follow up, 24% of patients had declined. Patients that declined were significantly older at onset of symptoms and first presentation to memory clinic, and took significantly more medications for physical illnesses. Patients that declined also performed significantly worse on Trail Making Test (TMT) B and Cambridge Cognitive Examination - Revised (CAMCOG-R) at baseline. Survival analysis identified key variables that predicted decline (later age of onset and later age at first assessment). CONCLUSIONS: Patients who present with subjective memory complaints and are over the age of 61 years are at high risk of cognitive decline and warrant an in-depth assessment and follow-up.

Attitudes of UK psychiatrists to the diagnosis of MCI in clinical practice.

BACKGROUND: Mild cognitive impairment (MCI) may represent a transitional stage between normal functioning and dementia. Following the initial criteria developed by Petersen et al. in 1999, which focused on memory deficit in the context of otherwise normal cognition and general functioning, the concept has evolved with the introduction of subtypes of MCI and improved understanding of etiology. Our aim was to investigate current practice as well as familiarity with and attitudes toward the concept of MCI amongst UK old age psychiatrists. METHOD: We sent an anonymized postal survey to all clinicians on the Royal College of Psychiatrists Old Age Psychiatry register. Questions covered attitudes toward the concept of MCI in addition to diagnostic criteria and assessment tools used. RESULTS: The response rate was 39% (453 of 1,154 questionnaires returned completed). The majority of respondents were consultants (83%) and 91% diagnosed MCI. Only 4.4% of the respondents thought that the concept of MCI was not useful and 79% of them required a memory complaint from either the patient or an informant for a diagnosis, but the majority did not have a specific cut-off on cognitive testing. Eighty-two percent reported that they required no or minimal impairment in activities of daily living for a diagnosis of MCI. The two most frequently used tools for assessment were the Mini-Mental State Examination and the Addenbrooke's Cognitive Examination-Revised. CONCLUSIONS: Our survey shows that in the United Kingdom, the term MCI has become part of everyday clinical practice in psychiatry, suggesting that clinicians find it a useful term to conceptualize the transitional stage between normal aging and dementia. However, there is variability in diagnostic practice.

Memory complaints with and without memory impairment: the impact of leukoaraiosis on cognition.

White matter alterations, leukoaraiosis (LA) on structural MRI, are associated with cognitive deficits and increased risk of dementia. LA may also impact on subjective memory complaints in otherwise healthy older adults. Little is known about the interplay between LA memory complaints and cognition. We investigated cognitive phenotypes associated with LA in 42 non-demented older adults categorized as having subjective cognitive complaints with no objective cognitive impairment-the subjective cognitive impairment group (SCI; n = 12), amnesic mild cognitive impairment (aMCI; n = 20), or healthy controls (HC; n = 11). We measured LA severity on MRI with a 40-point visual rating scale. Controlling for age and Mini-Mental State Examination (MMSE) score, analyses revealed multiple between-group differences. Follow-up linear regression models investigating the underlying contributors to each clinic group's cognitive profile indicated that LA contributed to learning slope variance (after accounting for age and MMSE) but only for the SCI group. Although the SCI group showed a significantly steeper learning slope when compared to HC and aMCI, increasing LA severity negatively impacted this group's rate of learning. This, in conjunction with the significant contribution of age on SCI learning slope performance variance suggests that greater LA burden at a younger age may contribute to subtle changes in learning for individuals with subjective cognitive complaints.

Dopaminergic imaging: clinical utility now and in the future.

Over the past ten years, dopaminergic imaging has become increasingly part of the assessment and diagnosis of dementia. There are numerous PET and SPECT ligands available that target different steps in the process of neurotransmission. Abnormalities in dopaminergic imaging measures are consistent features of dementia with Lewy bodies (DLB) and other parkinsonian syndromes, and can be used to facilitate diagnosis, particularly in distinguishing between DLB and Alzheimer's disease. This review summarizes present knowledge in this area and the implications for current and future clinical practice.

Ten years of cholinesterase inhibitors.

In this editorial we have summarised ten years of evidence relating to the use of cholinesterase inhibitors in Alzheimer's and other dementias. We have presented this evidence in the context of the evolution of public and professional awareness of dementia and its management and prescribing patterns over this time frame. We also briefly outline recent political and legal events surrounding the 2007 NICE guidance and the possible long-term impact of cholinesterase inhibitors on clinical practice. Whilst cholinesterase inhibitors continue to play a part in the management of Alzheimer's disease, it is possible that their most important legacy will be their contribution to the increased awareness and recognition of dementia as a neurodegenerative disease and the resulting transformation of old age psychiatry services.

Subjective cognitive impairment: increased prefrontal cortex activation compared to controls during an encoding task.

OBJECTIVE: Subjective cognitive impairment (SCI) has been proposed as a clinical stage which may precede mild cognitive impairment in the clinical continuum of AD, and is characterised by the presence of subjective memory complaints in the absence of objective cognitive deficits. Specific memory-related brain activation differences have been reported in mild cognitive impairment and in cognitively normal individuals at known genetic risk of AD; our objective was to determine whether similar differences are present in people with SCI. METHODS: We compared brain activation in a memory clinic sample of 10 SCI subjects and 10 controls during a verbal episodic memory encoding task using functional magnetic resonance imaging (fMRI). RESULTS: There were no differences between groups on measures of encoding success (recognition accuracy) nor was there evidence of altered semantic processing. Both groups activated left prefrontal cortex (PFC) and cerebellum during encoding. The SCI group also demonstrated activation in left medial temporal, occipitoparietal and medial frontal cortex. Group comparisons revealed increased activation in SCI in left PFC, where activation strength correlated with memory task performance. CONCLUSIONS: The activation differences reported in this study may reflect the employment of compensatory strategies in the face of early AD pathology, although a number of alternative explanations need to be considered. Further studies with larger samples may help to determine whether the observed activation changes are likely to be associated with early neuropathological processes or with other unrelated factors.

Parkinson's-adapted cognitive stimulation therapy: feasibility and acceptability in Lewy body spectrum disorders.

BACKGROUND: Drug-based therapeutic approaches for Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are moderately effective and not always tolerated. Tailoring psychosocial approaches in PDD and DLB may offer additional support and improve outcomes. We adapted home-based, care partner-delivered Cognitive Stimulation Therapy (CST) for individuals with PDD or DLB and their care partners (CST-PD). OBJECTIVES: To evaluate the feasibility, acceptability, and tolerability of CST-PD. METHODS: This randomised controlled trial used mixed methods, including a process evaluation. People with PDD, DLB or mild cognitive impairment in PD (PD-MCI) and their care partners were randomised to 12 weeks of treatment as usual (TAU) or CST-PD. Outcomes were feasibility of the study conduct (i.e., recruitment, retention rate) and acceptability and tolerability of the intervention. Measures included rating scales, researcher field notes, therapy diaries, and exploratory clinical and care partner efficacy measures. RESULTS: The recruitment target was met with 76 consenting participant-dyads. Retention in both arms was high at over 70%. More than 90% of dyads undertook discrete sessions greater than 20 min duration, but the average number of sessions completed was lower than the recommended dose. Acceptability ratings (i.e., interest, motivation and sense of achievement) of the intervention were high. Participants reported no serious adverse events related to the intervention. CONCLUSIONS: The field of psychosocial interventions for PDD and DLB is newly emerging, and we demonstrated that this type of intervention is acceptable and well tolerated. Evaluating its clinical effectiveness in a full-scale randomized controlled clinical trial is warranted. TRIAL REGISTRATION NUMBER: The trial is a psychosocial intervention with an allocated ISRCTN number 11455062.

Parkinson's-adapted cognitive stimulation therapy: a pilot randomized controlled clinical trial.

Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson's disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of 'CST-PD', which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant-dyads [PD-MCI (n = 15), PDD (n = 40), DLB (n = 21) and their care partners] to CST-PD or treatment as usual (TAU). CST-PD involves home-based cognitively stimulating and engaging activities delivered by a trained care partner. Exploratory outcomes at 12 weeks included cognition (Addenbrooke's Cognitive Evaluation; ACE-III), neuropsychiatric symptoms and function. In care partners, we assessed burden, stress and general health status. Relationship quality and quality of life were assessed in both dyad members. At 12 weeks, the ACE-III showed a nonstatistically significant improvement in the CST-PD group compared with the TAU group, although neuropsychiatric symptoms increased significantly in the former. In contrast, care partners' quality of life (d = 0.16) and relationship quality ('satisfaction', d = 0.01; 'positive interaction', d = 0.55) improved significantly in the CST-PD group, and care burden (d = 0.16) and stress (d = 0.05) were significantly lower. Qualitative findings in the CST-PD recipients revealed positive 'in the moment' responses to the intervention, supporting the quantitative results. In conclusion, care-partner-delivered CST-PD may improve a range of care-partner outcomes that are important in supporting home-based care. A full-scale follow-up RCT to evaluate clinical and cost effectiveness is warranted.

Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study.

OBJECTIVES: Dementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. DESIGN: In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. SETTING: Patients were recruited from 40 European centres. PARTICIPANTS: Subjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. OUTCOME MEASURES: The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). RESULTS: The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. CONCLUSIONS: DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.

Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine.

BACKGROUND: The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease. METHODS: Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure. RESULTS: 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12-170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes. CONCLUSIONS: The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.