Community memory screening as a strategy for recruiting older adults into Alzheimer's disease research.

BACKGROUND: Growing awareness of Alzheimer's disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memory Screening Day events provide free, brief cognitive screening aimed at those 65 years and older, and can serve as an opportunity to gauge participants' attitudes towards AD research and recruit them into ongoing research projects. METHODS: Over 6 single-day events in 2 years, more than 574 individuals were individually screened using the MoCA and a story recall task (immediate and delayed), given feedback about their performance, and introduced to AD research and opportunities to participate. RESULTS: Screening classified 297 individuals (52.0%) as having "No Decline," 192 (33.6%) as "Possible decline," and 82 (14.4%) as "Likely decline." Those with "Likely decline" were older and less educated, had more memory concerns, were more likely to be men, and were less likely to have a positive family history of dementia than those with "No Decline." Subsequent validation of screening procedures against a full clinical evaluation showed 72% classification accuracy with a skew towards over-calling Possible and Likely decline and thereby guiding questionable individuals to a more thorough evaluation. Of those screened, 378 (66%) agreed to additional research and consented to being listed in a research registry, and a majority (70-85%) of those consenting reported they were amenable to various AD research procedures including lumbar puncture, MRI, and autopsy. Overall, 19.1% of those screened met inclusion criteria for ongoing studies and were successfully recruited into AD research. CONCLUSIONS: Conducting a few concentrated community memory screening events each year may help meet the public's demand for brief assessment of memory concerns and can be a relatively effective and efficient recruitment strategy for AD research.

Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial.

Importance: Insulin modulates aspects of brain function relevant to Alzheimer disease and can be delivered to the brain using intranasal devices. To date, the use of intranasal insulin to treat persons with mild cognitive impairment and Alzheimer's disease dementia remains to be examined in a multi-site trial. Objective: To examine the feasibility, safety, and efficacy of intranasal insulin for the treatment of persons with mild cognitive impairment and Alzheimer disease dementia in a phase 2/3 multisite clinical trial. Design, Setting, and Participants: A randomized (1:1) double-blind clinical trial was conducted between 2014 and 2018. Participants received 40 IU of insulin or placebo for 12 months during the blinded phase, which was followed by a 6-month open-label extension phase. The clinical trial was conducted at 27 sites of the Alzheimer's Therapeutic Research Institute. A total of 432 adults were screened, and 144 adults were excluded. Inclusion criteria included adults aged 55 to 85 years with a diagnosis of amnestic mild cognitive impairment or Alzheimer disease (based on National Institute on Aging-Alzheimer Association criteria), a score of 20 or higher on the Mini-Mental State Examination, a clinical dementia rating of 0.5 or 1.0, and a delayed logical memory score within a specified range. A total of 289 participants were randomized. Among the first 49 participants, the first device (device 1) used to administer intranasal insulin treatment had inconsistent reliability. A new device (device 2) was used for the remaining 240 participants, who were designated the primary intention-to-treat population. Data were analyzed from August 2018 to March 2019. Interventions: Participants received 40 IU of insulin (Humulin-RU-100; Lilly) or placebo (diluent) daily for 12 months (blinded phase) followed by a 6-month open-label extension phase. Insulin was administered with 2 intranasal delivery devices. Main Outcomes and Measures: The primary outcome (mean score change on the Alzheimer Disease Assessment Scale-cognitive subscale 12) was evaluated at 3-month intervals. Secondary clinical outcomes were assessed at 6-month intervals. Cerebrospinal fluid collection and magnetic resonance imaging scans occurred at baseline and 12 months. Results: A total of 289 participants (155 men [54.6%]; mean [SD] age, 70.9 [7.1] years) were randomized. Of those, 260 participants completed the blinded phase, and 240 participants completed the open-label extension phase. For the first 49 participants, the first device used to administer treatment had inconsistent reliability. A second device was used for the remaining 240 participants (123 men [51.3%]; mean [SD] age, 70.8 [7.1] years), who were designated the primary intention-to-treat population. No differences were observed between treatment arms for the primary outcome (mean score change on ADAS-cog-12 from baseline to month 12) in the device 2 ITT cohort (0.0258 points; 95% CI, -1.771 to 1.822 points; P = .98) or for the other clinical or cerebrospinal fluid outcomes in the primary (second device) intention-to-treat analysis. No clinically important adverse events were associated with treatment. Conclusions and Relevance: In this study, no cognitive or functional benefits were observed with intranasal insulin treatment over a 12-month period among the primary intention-to-treat cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT01767909.

Temporal sequence learning in healthy aging and amnestic mild cognitive impairment.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Temporal sequence learning is a critical aspect of episodic memory that may be dependent on the temporal and frontal lobes. Because amnestic mild cognitive impairment (aMCI) and normal aging may result in changes within the temporal and frontal lobes, the present study investigated temporal sequence learning in patients with aMCI, cognitively normal older adults, and young adults. METHODS: On each trial of a temporal sequence task, circles appeared one at a time at the end of each arm of a computerized radial eight-arm maze. Participants were asked to reproduce the temporal sequence by placing numbered circles (1 to 8) on the arms of the eight-arm maze. Participants were presented with the same fixed sequence on each trial until the sequence was replicated without any errors, or until 15 trials were presented. RESULTS: Individuals with aMCI required significantly more trials to learn the temporal sequence compared with older adults (p < .05). Older adults required significantly more trials to learn the sequence than young adults (p < .05). Older adults and individuals with aMCI committed significantly more Trial 1 errors (p < .05) than young adults; however, there were no significant differences between the aMCI and older adult groups on Trial 1. CONCLUSION: The results suggest that temporal sequence learning deficits are detectable in aMCI. These deficits may disrupt a number of cognitive processes, such as episodic memory, that are important for the execution of daily activities. The results suggest that although temporal sequence learning declines with normal aging, this decline is greater in individuals who have a diagnosis of aMCI and are at higher risk for developing Alzheimer's disease.

When help becomes a hindrance: mental health referral systems as barriers to care for primary care physicians treating patients with Alzheimer's disease.

OBJECTIVES: To describe structural barriers to mental health specialists and consequences of these barriers to care for patients with dementia and neuropsychological symptoms and their primary care physicians (PCPs). DESIGN: Cross-sectional qualitative interview study of PCPs. SETTING: Physicians' offices, primarily managed care. PARTICIPANTS: Forty PCPs in Northern California. MEASUREMENTS: Open-ended interviews lasted 30-60 minutes. The interview guide covered clinician background, practice setting, clinical care of a particular patient, and general approach to managing patients with Alzheimer disease or related dementias.Interviews were transcribed and themes reflecting referrals identified. RESULTS: Ninety-three percentage of the PCPs described problematic access to and communication with mental health specialists (in particular psychiatrists and neuropsychologists) as impediments to effective care for dementia patients. Thematic analysis identified structural barriers to mental health referrals ranging from problems with managed care and reimbursement policies to lack of trained providers and poor geographic distribution of specialists. Structural barriers compromised care for patients with dementia because the barriers limited PCP treatment options, and resources, impacted office staff and time with other patients, impeded and delayed care, and fostered poor communication and lack of coordinated care. Negative consequences for PCPs included increased frustration,conflict, and burnout. CONCLUSION: PCPs viewed problems created by onerous referral systems, such as mental health carve outs, as particularly burdensome for elderly patients with comorbid dementia and neuropsychiatric problems. These problems were cited by PCPs across different types of practice settings. PCPs managed treatment of neurobehavioral symptoms as best they could despite lack of specialist support.

Deterioration of visual-perceptual organization ability in Alzheimer's disease.

Although deterioration of higher-order visual information processing abilities occurs in Alzheimer's disease (AD), few cross-sectional or longitudinal studies have systematically examined this deficit. The performance of 135 patients with probable AD and 97 matched normal control (NC) participants were compared on a structured test of perceptual organization ability, the Hooper Visual Organization Test (VOT). Both the standard VOT score and a derived score that corrected for anomia were significantly lower for AD patients than for NC participants, but neither score was particularly effective at distinguishing between the groups. The derived VOT score proved to be a more effective measure of visuospatial functioning than the standard VOT score as it loaded with other visuospatial tests in a principal components analysis while the standard score loaded with language tests. The VOT was sensitive to severity of dementia in the AD patients. Longitudinal assessment of 37 of the AD patients and 46 NC participants revealed significant decline over one year in the VOT scores of AD patients, but not in those of NC participants. These results indicate that higher-order visual information processing is impaired in patients with AD and gradually deteriorates with disease progression. This deficit may not be a particularly salient early marker of the disease, but it may be useful in tracking disease course.

Effectiveness of support groups for people with mild to moderate Alzheimer's disease: an evaluative survey.

Support groups can provide a forum for socialization and learning for people with mild to moderate Alzheimer's disease. The aim of this study was to evaluate the effectiveness of these groups based on participant feedback. A survey questionnaire was administered to 70 support group participants with Alzheimer's disease from 8 well-established groups across the United States. Participants reported on the educational value, positive socialization, and improved ability to cope with symptoms and to accept the diagnosis as a result of participating in a support group. These reported outcomes suggest the importance of creating more sensitive measures to better evaluate the effectiveness of support groups and other educational or social support programs for persons with dementia.

Identification of Alzheimer disease risk by functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials. OBJECTIVE: To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults. DESIGN: Cross-sectional case-control study. SETTING: University of California, San Diego, Alzheimer Disease Research Center participants and San Diego community volunteers. PARTICIPANTS: Twenty cognitively normal individuals (10 high risk and 10 low risk), aged 58 to 65 years, were divided into 2 groups based on the presence or absence of the apolipoprotein E epsilon4 allele and a positive family history of AD. MAIN OUTCOME MEASURES: Word pairs were presented in a blocked design alternating between conditions of novel pairs, repeated pairs, and fixation. Whole-brain differences in blood oxygenation level-dependent brain responses between conditions were compared across risk groups. RESULTS: Compared with the low-risk group, the high-risk group showed many areas of differential blood oxygenation level-dependent response in regions commonly associated with AD pathology (eg, the left medial temporal lobe). Furthermore, different patterns of association between left medial temporal lobe activity and memory performance were demonstrated. CONCLUSIONS: Results support a theory of up-regulation in neuronal memory systems in people at risk for AD many years before the typical age at disease onset. They further demonstrate that functional magnetic resonance imaging is a viable technique to identify persons at risk for AD.