Korean Addenbrooke's Cognitive Examination Revised (K‐ACER) for differential diagnosis of Alzheimer's disease and subcortical ischemic vascular dementia

Aim: Sensitive, specific neuropsychological screening tests, such as the Addenbrooke's Cognitive Examination Revised (ACE‐R), are essential for dementia diagnosis. We aimed to validate the use of the Korean version of ACE‐R (K‐ACER) to differentiate Alzheimer's disease (AD) from subcortical ischemic vascular dementia (SIVD). Methods: Standard tests for dementia screening were applied to 156 subjects (84 controls, 30 AD, 42 SIVD), and total and sub‐domain scores on the K‐ACER, as well as the sub‐domain ratio (VLOM), were compared. Results: The reliability of the K‐ACER was very good (α‐coefficient 0.84), and cut‐off score for dementia was determined (cut‐off value 78, sensitivity 0.93, specificity 0.95). The likelihood ratio for dementia was calculated as between 78 and 82. At a cut‐off of 78, the likelihood of dementia was 18.6:1. Although a comparison of K‐ACER scores between AD and SIVD patients revealed significant differences in verbal fluency, language domain and VLOM ratio, sensitivity and specificity for differential diagnosis between AD and SVID proved less accurate. Conclusion: The K‐ACER is a rapid, sensitive and specific dementia screening test. Though sub‐domains of items may be useful for differentiating between AD and SIVD, sensitivity and specificity is less accurate than dementia screening itself. Geriatr Gerontol Int 2010; 10: 295–301.     

Amyloid‐ß‐directed immunotherapy for Alzheimer's disease

Current treatment options for Alzheimer's disease (AD) are limited to medications that reduce dementia symptoms. Given the rapidly ageing populations in most areas of the world, new therapeutic interventions for AD are urgently needed. In recent years, a number of drug candidates targeting the amyloid‐ß (Aß) peptide have advanced into clinical trials; however, most have failed because of safety issues or lack of efficacy. The Aß peptide is central to the pathogenesis, and immunotherapy against Aß has attracted considerable interest. It offers the possibility to reach the target with highly specific drugs. Active immunization and passive immunization have been the most widely studied approaches to immunotherapy of AD. A favourable aspect of active immunization is the capacity for a small number of vaccinations to generate a prolonged antibody response. A potential disadvantage is the variability in the antibody response across patients. The potential advantages of passive immunotherapy include the reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti‐amyloid immunotherapy remains one of the most promising emerging strategies for developing disease‐modifying treatments for AD. In this review, we examine the presently ongoing Aß‐directed immunotherapies that have passed clinical development Phase IIa.     

Cognitive dysfunction: An emerging concept of a new diabetic complication in the elderly

The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is likely to continue. Recent advances suggest that T2DM is a risk factor for cognitive decline. We are now encountering novel complications of T2DM, namely cognitive dysfunction and dementia. Although the treatment strategy for diabetic patients with neurocognitive dysfunction has received a great deal of attention, the appropriate level of glycemic control for the prevention of the development and/or progression of cognitive decline in elderly diabetic patients remains to be elucidated. Another issue in diabetic treatment in patients with cognitive dysfunction is the selection of medicines. The best choice and combination of antidiabetic medications for the preservation of cognition should also be studied. Ample studies suggest that exercise helps to preserve cognitive function, although existing evidence does not necessarily indicate its effectiveness exclusively in diabetic patients. Exercise is a helpful non‐pharmacological therapy. Considering the progressive aging of the worldwide population, more research to investigate the best way to manage this population is important. Geriatr Gerontol Int 2012; ••: ••–•• .     

Montefiore‐Einstein Center for the Aging Brain: Preliminary Data

Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one‐year experience with outpatient based dementia care at the Montefiore‐Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non‐pharmacological treatments as appropriate, and the facilitation of access to clinical trials . The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self‐identified ethnicity of patients included Caucasian (26%), African‐American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one‐year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians.     

Screening for cognitive impairment in an elderly veteran population: acceptability and results using different versions of the Mini-Cog

OBJECTIVES: To assess the feasibility of cognitive screening in older veterans presenting for routine primary care. DESIGN: Quality improvement initiative. SETTING: Seven Veterans Affairs Medical Centers. PARTICIPANTS: Veterans aged 70 and older without a prior diagnosis of cognitive impairment. MEASUREMENTS: Scores from 16 different versions of the Mini‐Cog, a 5‐point cognitive screen consisting of three‐word recall (0–3 points) with a clock‐drawing interference task (0 or 2 points). Five word lists were paired with three clock times and randomly ordered for presentation with the original Mini‐Cog version. The conventional dementia screening cut point was increased to maximize sensitivity; to pass, patients had to draw the clock correctly and recall at least two of three words (score 4 or 5/5). RESULTS: Administering the Mini‐Cog took 90 to 180 seconds. Of 8,342 veterans approached, 8,063 (96.7%) agreed to be screened; 2,081 (25.8%) scored less than 4 out of 5. Scores declined with age, but age did not predict pass or fail. Different word lists produced different screen failure rates, ranging from 21.2% to 33.4%. Five dementia specialists were unable to distinguish harder from easier lists. Different clock times accounted for 2% or less of the difference in failure rates. CONCLUSION: The Mini‐Cog was quick and well accepted by older veterans. Many with no prior documentation of cognitive impairment failed the screen. Failure rates varied with the word list used, revealing that even apparently minor changes in test items affect screen results. Additional study is needed to establish the value of cognitive screening in shaping primary care of older veterans.     

Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment

Background/Objectives

Behavioral problems in individuals with Alzheimer's disease (AD ) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI ).

Design

Longitudinal observational cohort study.

Setting

Academic medical center.

Participants

Members of an apolipoprotein E (APOE ) ?4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory—Revised (NEO ‐PI ‐R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO ‐PI ‐R administrations.

Intervention

Longitudinal administration of the NEO ‐PI ‐R and neuropsychological test battery.

Measurements

Change in NEO ‐PI ‐R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow‐up duration in nontransitioners.

Results

NEO ‐PI ‐R neuroticism T‐scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI ) = 0.9–4.9 vs 0, 95% CI = ?0.7–0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (?4.8, 95% CI = ?7.3 to ?2.4 vs ?1.0, 95% CI = ?1.6 to ?0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude.

Conclusion

Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.

     

Frequency and Correlates of Caregiver‐Reported Sleep Disturbances in a Sample of Persons with Early Dementia

OBJECTIVES: To identify sleep disturbances in participants with subtypes of dementia and explore clinical correlates. DESIGN: Cross‐sectional. SETTING: Outpatient clinics in western Norway and the Mayo Clinic Study of Aging, Olmsted County, Minnesota. PARTICIPANTS: One hundred fifty‐one community‐dwelling western Norway residents referred for geriatric medicine, geriatric psychiatry or neurology evaluation and 420 participants without dementia from the Mayo Clinic Study of Aging. MEASUREMENTS: Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Mayo Sleep Questionnaire, an interview to detect sleep disturbances, was administered to diagnose probable rapid eye movement (REM) sleep behavior disorder, probable periodic leg movements during sleep, probable restless legs syndrome, probable sleepwalking, probable sleep‐related leg cramps, probable obstructive sleep apnea, and excessive daytime sleepiness. Insomnia was assessed using the Neuropsychiatric Inventory, an interview to detect neuropsychiatric symptoms in dementia. RESULTS: Seventy‐one percent of the participants with dementia and 55.7% of control participants had sleep disturbances (P=.001). Most frequently reported in the mild dementia participants were insomnia (29.9%), probable sleep‐related leg cramps (24.1%), excessive daytime sleepiness (22.6%), probable restless legs syndrome (20.7%), and probable REM sleep behavior disorder (18.5%). There were more sleep‐related problems reported in participants with Lewy body dementias (LBD) (dementia with Lewy bodies and Parkinson's disease dementia) than in those with Alzheimer's disease (P=.008). Having any sleep disorder correlated with depression (P=.03) and anxiety (P=.02). CONCLUSION: Sleep problems are common in dementia, particularly in subjects with LBD, and are associated with psychiatric symptoms. Further research is needed to understand these associations and identify treatment strategies.