Community recruitment of underrepresented populations to the AHEAD 3‐45 preclinical AD trial using novel partnerships with nursing and community‐based organizations: Lessons and outcomes

IntroductionAlzheimer's disease (AD) disproportionately affects minoritized populations who remain underrepresented in AD trials.MethodsWe partnered with local nursing community-based organizations to implement a culturally tailored educational intervention and recruit Hispanic/Latino American, Filipino American, and Korean American adults aged 55 to 80 for the AHEAD study, a preclinical AD trial, at the University of California, Irvine.ResultsWe engaged 654 individuals across 21 events, leading to 71 prescreenings: 21.1% Filipino, 11.2% Hispanic/Latino, and 67.6% Korean adults. Ineligibility due to age and language barriers was common among Hispanic/Latino and Korean adults, respectively. Filipino adults often withdrew interest or were lost to follow-up. Ultimately, 25 participants enrolled: eight Filipino, two Hispanic/Latino, and 15 Korean adults. Tailored, culturally relevant content significantly contributed to the engagement success.DiscussionThis study demonstrates the value and impact of novel partnerships with health-related provider organizations that provide trusted care and access to underrepresented communities.HighlightsSix hundred and fifty four underrepresented individuals were reached, and 25 enrolled in the AHEAD 3-45 trial. Twenty-one community events were held via partnerships with nursing and community organizations. The study engaged 21% Filipino, 11% Hispanic/Latino, 68% Korean adults. Community-Based Participatory Research (CBPR) principles enhanced the recruitment process. Transparent communication and joint planning were key

Late‐life emergence of neuropsychiatric symptoms and risk of cognitive impairment in cognitively unimpaired individuals

IntroductionNeuropsychiatric symptoms (NPS) often precede cognitive impairment. We investigated the longitudinal relationship between emergent, significant NPS and cognitive decline in cognitively unimpaired older adults. We also assessed the combined effect of NPS and Alzheimer's disease (AD) biomarkers on subsequent cognitive impairment.MethodsWe included 190 cognitively unimpaired participants without NPS at baseline and tracked the emergence of significant NPS and conversion to mild cognitive impairment (MCI).ResultsThe average follow-up was 8.1 years, with a maximum of 19 years. Participants with emergent, significant NPS had a 3.92-fold higher risk of cognitive impairment than those without (95% confidence interval 1.51-10.17, P = 0.005). Individuals with NPS and AD biomarkers showed a markedly higher conversion rate to MCI than those with neither risk factor.DiscussionOur findings emphasize the role of emergent, significant NPS as early clinical indicators of cognitive impairment and suggest the potential benefit of incorporating clinical symptoms and neurobiological markers to better predict cognitive course.HighlightsWe investigated the association between emergent neuropsychiatric symptoms (NPS) and conversion to mild cognitive impairment (MCI). One hundred ninety cognitively unimpaired individuals were followed for an average of 8.1 years. Emergent NPS increased the risk of conversion to MCI > 3-fold. After emergent NPS, cognitive test performance declined. The co-occurrence of NPS and high cerebrospinal fluid phosphorylated tau181 amplified the risk of MCI

Metabolic Changes Associated With Second-Generation Antipsychotic Use in Alzheimer’s Disease Patients: The CATIE-AD Study

The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer’s disease are frequently treated with these antipsychotics but there is little data available on their metabolic effects

Cognitive neuroscience of delusions in aging

Assessments and clinical understanding of late-onset delusions in the elderly are inconsistent and often incomplete. In this review, we consider the prevalence, neurobehavioral features, and neuroanatomic correlations of delusions in elderly persons – those with documented cognitive decline and those with no evidence of cognitive decline. Both groups exhibit a common phenotype: delusions are either of persecution or of misidentification. Late-onset delusions show a nearly complete absence of the grandiose, mystical, or erotomanic content typical of early onset psychoses. Absent also from both elderly populations are formal thought disorders, thought insertions, and delusions of external control. Neuroimaging and behavioral studies suggest a frontotemporal localization of delusions in the elderly, with right hemispheric lateralization in delusional misidentification and left lateralization in delusions of persecution. We propose that delusions in the elderly reflect a common neuroanatomic and functional phenotype, and we discuss applications of our proposal to diagnosis and treatment

Amyloid-β predominant Alzheimer’s disease neuropathologic change

Different subsets of Alzheimer's disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer's Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele