A direct comparison of errorless and errorful therapy for object name relearning in Alzheimer's disease.

Developing rehabilitation techniques to combat cognitive decline is a key goal of healthcare strategies aimed at promoting increased longevity and better quality of life for individuals with Alzheimer's disease (AD). In AD, problems with episodic memory and word-finding greatly affect everyday life and, as such, these symptoms provide a clear clinical target for therapeutic interventions. Errorless learning (EL) has been proposed as a particularly effective technique for relearning in individuals with memory dysfunction, including AD. However, EL learning has rarely been directly contrasted with other more traditional trial-and-error techniques (errorful learning or EF) in individuals with AD, especially in the context of alleviating word-finding problems. In the current study, we directly contrasted the therapeutic gains of an EL learning paradigm (consisting of reading/repetition of object names) with an EF learning technique (comprised of phonemic/orthographic cueing) in eight mild to moderate AD patients with pronounced anomia. Both techniques were administered concurrently in sessions run twice a week over a five-week period. Therapeutic gains were assessed at one week and five weeks post-intervention using confrontation naming. Our results suggest that, both at the group and individual patient level, EL and EF techniques were equally effective. Correlational analyses of overall therapy gains and background assessments of patient neuropsychology revealed that individuals with better scores on measures of semantic memory, pre-intervention naming, and recognition memory demonstrated larger therapy gains. No individual patient showed a significant advantage for EL over EF learning, however, for patients that showed a numerical advantage in this direction. These results suggest that either EL or EF therapy can be used to alleviate word-finding problems in AD.

Age at onset and vascular pathology in late-life depression.

OBJECTIVE: There is considerable evidence to suggest that late-onset depression may be etiologically distinct from early-onset depression. The aim of this study was to compare vascular function and magnetic resonance imaging-defined brain ischemic changes between early-onset depressed (EOD) and late-onset depressed (LOD) subjects. DESIGN: Case-control study. PARTICIPANTS: Twenty-five subjects with late-life depression recruited from secondary care were divided into groups with EOD (<60 years, 11 subjects) and LOD (>60 years, 14 subjects). MEASURES: All subjects underwent a variety of vascular assessments including pulse wave analysis, pulse wave velocity, carotid intima media thickness (IMT), and magnetic resonance imaging of the brain to assess white matter hyperintensities. RESULTS: The mean age of LOD subjects was 71.3 ± 4.0 years and EOD was 73.6 ± 4.7 years (p = NS). There were no baseline differences in vascular risk or sociodemographic variables. LOD subjects had significantly higher common carotid IMT (EOD: 0.06 [0.01]; LOD: 0.09 [0.02], p = 0.02), carotid plaques (EOD: 2.1 [1.1]; LOD: 5.4 [3.9], p = 0.02), and peripheral augmentation index (EOD: 81.7 [7.9]; LOD: 96.2 [21.6], p = 0.04) when compared with early-onset subjects, indicating more vascular pathology. There were no group differences in white matter hyperintensities. Age at onset of depression was positively correlated with peripheral augmentation index, common carotid IMT, and plaque index. CONCLUSION: This study suggests that elderly subjects with LOD have greater vascular impairment than those with an early-onset illness. Whether preventing vascular disease at an earlier age may decrease the risk of last onset depression is a potential area for future research.

Vascular function in older adults with depressive disorder.

BACKGROUND: Cerebrovascular disease plays an important role in depressive disorder, especially in older adults. An understanding of vascular function in depression is important etiologically and to develop innovative treatments that may improve prognosis by ameliorating vascular damage. METHODS: This study assessed endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds in 25 elderly subjects with depressive disorder compared with 21 nondepressed control subjects. Subjects underwent pulse wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging. A subset (16 patients and 15 control subjects) had assessment of biopsied small artery dilatation to acetylcholine to further assess endothelial function. RESULTS: The mean sample age was 72.4 years with an average age at onset for depression of 60 years. Mean carotid intima media thickness was significantly higher in depressed subjects (p < .01). Pulse wave velocity was 1.6 m/sec higher in depressed subjects (borderline significance). There was a significant reduction in the dilatation response to acetylcholine in preconstricted small arteries (p = .01). On magnetic resonance imaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia (p = .01). Depressed subjects had greater volume of white matter lesions in all regions, but this did not reach statistical significance. There were no baseline differences in vascular risk. CONCLUSIONS: Depression in the elderly is associated with poorer endothelial function and more atherosclerosis. This is associated with a greater white matter hyperintensities lesion load and basal ganglia microangiopathy. The use of vasoprotective drugs to improve endothelial function or retard atherosclerosis as depression-modifying agents should be explored.

Putting brain training to the test.

'Brain training', or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals and preschool children, and video-game players outperform non-players on some tests of visual attention. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.

Donepezil for the treatment of agitation in Alzheimer's disease.

BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear. METHODS: We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks. RESULTS: There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], -0.06; 95% confidence interval [CI], -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change. CONCLUSIONS: In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324 [ClinicalTrials.gov].).

Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy.

There is growing evidence that microvascular angiopathy (MVA) plays an important role in the development of dementia and affective disorders in older people. At currently available image resolutions it is not possible to image directly the vascular changes associated with MVA, but the effects on blood and cerebrospinal fluid (CSF) flow may be detectable. The aim of this study was to investigate a potential biomarker for MVA based on MRI of abnormalities in CSF flow. Since there is considerable indirect evidence that treatment resistance in late-onset depressive disorder is related to MVA, we assessed the method in a group of 22 normal volunteers and 29 patients with responsive (N=21) or treatment-resistant (N=8) late-onset depressive disorder. Single-slice quantified phase-contrast (PC) images of cerebral blood and CSF flow were collected at 15 points over a cardiac cycle, and the resulting flow curves were parameterized. Significant differences in the CSF flow (width of systolic flow peak and diastolic flow volume, both P<0.01) through the cerebral aqueduct were observed for the group of treatment-resistant patients when compared to age matched controls. No significant difference was observed for a group of 21 patients with treatment-responsive depression. The findings support the hypothesis that MR measurement of CSF flow abnormalities provides a biomarker of MVA, and thus could have application in a wide range of age-related diseases.