Barry W. Rovner

Language dysfunction in early- and late-onset possible Alzheimer's disease

Disproportionate involvement of language has been claimed to be a distinguishing feature of Alzheimers disease (AD) with onset before age 65. We tested this hypothesis in a group of 133 patients with possible AD by NINCDS criteria. Sixty-one had onset of symptoms prior to age 65; the remaining 72, at 65 or later. The two groups were well matched on overall dementia severity as measured by the Mini-Mental State Exam. Using standardized tests, we did not find any significant differences in the severity of language dysfunction between the two groups, particularly after controlling for greater attention/ concentration deficits in the early-onset group. Previous reports of differences in language dysfunction between early- and late-onset AD may have been due to small sample sizes and nonstandardized testing.

Low Vision Depression Prevention Trial in Age-Related Macular Degeneration: A Randomized Clinical Trial

PURPOSEnTo compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD).nnnDESIGNnSingle-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months.nnnPARTICIPANTSnPatients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188).nnnINTERVENTIONSnBefore randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention.nnnMAIN OUTCOME MEASURESnThe Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes).nnnRESULTSnAt 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life.nnnCONCLUSIONSnAn integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry, rehabilitation, psychiatry, and behavioral psychology may prevent depression in this population.

A phase 2 study of tramiprosate for cerebral amyloid angiopathy.

Background and PurposeNo treatments have been identified to lower the risk of intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). A potential approach to prevention is the use of agents that interfere with the pathogenic cascade initiated by the β-amyloid peptide (Aβ). Tramiprosate (3-amino-1-propanesulfonic acid) is a candidate molecule shown in preclinical studies to reduce CAA in a transgenic mouse model. MethodsWe performed a 5-center phase 2 double-blinded trial to evaluate the safety, tolerability, and pharmacokinetics of tramiprosate in subjects with lobar intracerebral hemorrhage. Twenty-four subjects age ≥55 years with possible or probable CAA were randomized to receive 12 weeks of tramiprosate at 1 of 3 oral doses (50, 100, or 150u2009mg twice daily). Subjects were followed for clinical adverse effects, laboratory, vital sign, electrocardiogram, cognitive, or functional changes, appearance of new symptomatic or asymptomatic hemorrhages, and pharmacokinetic parameters. ResultsEnrolled subjects were younger (mean age 70.8±5.4, range 61 to 78) and had more advanced baseline disease (measured by number of previous hemorrhages) than consecutive subjects in a CAA natural history cohort. No concerning safety issues were encountered with treatment. Nausea and vomiting were the most common adverse events and were more frequent at high doses. Nine subjects had new symptomatic or asymptomatic hemorrhages during treatment; all occurred in subjects with advanced baseline disease, with no apparent effect of drug dosing assignment. ConclusionsThese data suggest that tramiprosate can be given safely to subjects with suspected CAA and support future efficacy trials.

Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimers disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimers disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society.

Cultural diversity and views on Alzheimer disease in older African Americans.

Cultural constructs prevalent in older African Americans may influence their risk perceptions and knowledge of Alzheimer disease (AD). To examine this issue, we administered 3 sociocultural scales, the AD Knowledge Scale, and a Risk Perception questionnaire to 271 older African Americans who were recruited from a large community senior center and local churches. Higher Present Time Orientation was significantly related to perceptions of having little control over risks to health (P=0.004), God’s Will in determining AD (P=0.001), and lower AD knowledge (P<0.0001) and marginally related to having little control over developing AD (P=0.052). Religiosity was marginally related to having little control over risks to health (P=0.055) and getting AD (P=0.057). Post hoc intergroup comparisons found significant differences in the highest versus lowest scoring Religiosity groups. There were no significant differences by Future Time Orientation. Most subjects (57.6%) were unaware that African Americans were at higher risk for AD than whites. These data indicate that cultural diversity within older African Americans may shape health perceptions and knowledge of AD. This diversity may contribute to disparities in the detection and treatment of AD in this high-risk population.

Underutilization of Physical and Mental Health Services Prior to Nursing Home Admission

The authors interviewed the families of 420 nursing home admissions to examine the relationship between patients need for nursing and mental health services and their use of these services prior to nursing home placement. Although the majority of demented and nondemented patients needed help with activities of daily living, and many needed help with behavioral disorders, fewer than one-third of the families of these patients used community nursing and mental health services for these problems. Increased awareness of the potential value of and improved access to these services may postpone or prevent nursing home placement.