Risk of neurodegenerative disease or dementia in adults with attention-deficit/hyperactivity disorder: a systematic review

Purpose of reviewSeveral psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, has been understudied in relation to dementia risk. We summarized existing literature investigating the risk of incident neurodegenerative disease or dementia associated with ADHD.Recent findingsWe searched five databases for cohort, case–control, and clinical trial studies investigating associations between ADHD and neurodegenerative diseases/dementia in May 2023. Study characteristics were extracted by two independent raters, and risk of bias was assessed using the Newcastle Ottawa Scale. Search terms yielded 2,137 articles, and seven studies (five cohort and two case–control studies) ultimately met inclusion criteria. Studies examined the following types of neurodegeneration: all-cause dementia, Alzheimer’s disease, Parkinson’s and Lewy body diseases, vascular dementia, and mild cognitive impairment. Heterogeneity in study methodology, particularly covariates used in analyses and types of ratios for risk reported, prevented a meta-analysis and data were therefore summarized as a narrative synthesis. The majority of studies (4/7) demonstrated an overall low risk of bias.SummaryThe current literature on risk of developing a neurodegenerative disease in ADHD is limited. Although the studies identified present evidence for a link between ADHD and subsequent development of dementia, the magnitude of the direct effect of ADHD on neurodegeneration is yet to be determined and better empirically designed studies are first needed. Furthermore, the mechanism of how or why ADHD is associated with an increased risk of developing a neurocognitive disorder is still unclear and should be explored in future studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348976, the PROSPERO number is CRD42022348976

White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer\u27s disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

Adult ADHD: Risk Factor for Dementia or Phenotypic Mimic?

Attention-deficit hyperactivity disorder (ADHD) has historically been considered a disorder of childhood and adolescence. However, it is now recognized that ADHD symptoms persist into adulthood in up to 60% of individuals. Some of the cognitive symptoms that characterize ADHD (inability to provide sustained attention or mental effort, difficulty organizing or multi-tasking, forgetfulness) may closely resemble symptoms of prodromal dementia, also often referred to as mild cognitive impairment (MCI), particularly in patients over age 50. In addition to the overlap in cognitive symptoms, adults with ADHD and those with MCI may also share a number of behavioral and psychiatric symptoms, including sleep disturbances, depression, and anxiety. As a result, both syndromes may be difficult to distinguish clinically in older patients, particularly those who present to memory clinics with subjective cognitive complaints and fear the onset of a neurodegenerative process: is it ADHD, MCI, or both? Currently, it is unclear whether ADHD is associated with incipient dementia or is being misdiagnosed as MCI due to symptom overlap, as there exist data supporting either possibility. Here, we aim to elucidate this issue by outlining three hypothetical ways in which ADHD and MCI might relate to each other, providing an overview of the evidence relevant to each hypothesis, and delineating areas for future research. This is a question of considerable importance, with implications for improved diagnostic specificity of early dementia, improved accuracy of disease prevalence estimates, and better identification of individuals for targeted treatment

Predicting Alzheimer's disease development: a comparison of cognitive criteria and associated neuroimaging biomarkers

Abstract Introduction The definition of “objective cognitive impairment” in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer’s disease (AD) from baseline to 24 months. Methods The sensitivity and specificity of six methods of defining episodic memory impairment (< −1, −1.5 or −2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer’s Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOEε4 status) was investigated using logistic regression. Results Baseline scores < −1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE ε4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < −1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = −15.97, SE = 7.58, p = .035), and APOEε4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < −2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE ε4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy. Conclusions Episodic memory impairment in MCI should be defined as scores < −1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE ε4 status can further improve prediction

Data_Sheet_1_Risk of neurodegenerative disease or dementia in adults with attention-deficit/hyperactivity disorder: a systematic review.docx

Purpose of reviewSeveral psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, has been understudied in relation to dementia risk. We summarized existing literature investigating the risk of incident neurodegenerative disease or dementia associated with ADHD.Recent findingsWe searched five databases for cohort, case–control, and clinical trial studies investigating associations between ADHD and neurodegenerative diseases/dementia in May 2023. Study characteristics were extracted by two independent raters, and risk of bias was assessed using the Newcastle Ottawa Scale. Search terms yielded 2,137 articles, and seven studies (five cohort and two case–control studies) ultimately met inclusion criteria. Studies examined the following types of neurodegeneration: all-cause dementia, Alzheimer’s disease, Parkinson’s and Lewy body diseases, vascular dementia, and mild cognitive impairment. Heterogeneity in study methodology, particularly covariates used in analyses and types of ratios for risk reported, prevented a meta-analysis and data were therefore summarized as a narrative synthesis. The majority of studies (4/7) demonstrated an overall low risk of bias.SummaryThe current literature on risk of developing a neurodegenerative disease in ADHD is limited. Although the studies identified present evidence for a link between ADHD and subsequent development of dementia, the magnitude of the direct effect of ADHD on neurodegeneration is yet to be determined and better empirically designed studies are first needed. Furthermore, the mechanism of how or why ADHD is associated with an increased risk of developing a neurocognitive disorder is still unclear and should be explored in future studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348976, the PROSPERO number is CRD42022348976.</p