Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Early and late contingent negative variation (CNV) reflect different aspects of deficits in schizophrenia.

Abnormal reward processing and psychomotor slowing are well-known in schizophrenia (SZ). As a slow frontocentral potential, contingent negative variation (CNV) is associated with anticipatory attention, motivation and motor planning. The present study aims to evaluate the early and late amplitude and latencies of CNV in patients with SZ compared to healthy controls during a reward processing task and to show its association with clinical symptoms. We recruited 21 patients with SZ and 22 healthy controls to compare early and late CNV amplitude and latency values during a Monetary Incentive Delay (MID) Task between groups. Patients' symptom severity, levels of negative symptoms and depressive symptoms were assessed. Clinical features of the patients were further examined for their relation with CNV components. In conclusion, we found decreased early CNV amplitudes in SZ during the reward condition. They also displayed diminished and shortened late CNV responses for incentive cues, specifically at the central location. Furthermore, early CNV amplitudes exhibited a significant correlation with positive symptoms. Both CNV latencies were linked with medication dosage and the behavioural outcomes of the MID task. We revealed that early and late CNV exhibit different functions in neurophysiology and correspond to various facets of the deficits observed in patients. Our findings also emphasized that slow cortical potentials are indicative of deficient motivational processes as well as impaired reaction preparation in SZ. To gain a deeper understanding of the cognitive and motor impairments associated with psychosis, future studies must compare the effects of CNV in the early and late phases.

Reduced Reward Processing in Schizophrenia: A Comprehensive EEG Event-Related Oscillation Study.

It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia (SZ). Reduced reward anticipation has been suggested as a core symptom of SZ. The present study aims to evaluate the event-related oscillations (EROs) delta, theta, alpha, beta, and gamma in patients with SZ during the Monetary Incentive Delay (MID) task, which elicits the neural activity of reward processing. Twenty-one patients with SZ and twenty-two demographically matched healthy controls were included in the study. EROs were compared between groups and correlation analyses were conducted to determine a possible relationship between clinical scores and ERO values. Compared with healthy controls, the SZ group had reduced (1) delta and theta amplitudes in the reward condition (2) total beta and non-incentive cue-related beta amplitudes, and (3) incentive cue-related frontal gamma amplitudes. These reductions can be interpreted as impaired dopaminergic neurotransmission and disrupted cognitive functioning in the reward processing of SZ. In contrast, SZ patients showed higher incentive cue-related theta and occipital gamma amplitudes compared to controls. These increments may reflect negative symptoms in SZ. Moreover, theta amplitudes showed a negative correlation with Calgary Depression Scale for Schizophrenia scores and a positive correlation with attentional impulsivity. This is the first study showing the impairments of SZ patients in EROs from delta to gamma frequency bands compared with healthy controls during reward anticipation. Being the first comprehensive study, our results can be interpreted as providing evidence for disrupted brain dynamics in the reward processing of SZ studied by EROs. It may become possible to help patients' wellness by improving our understanding of reward processing in schizophrenia and developing innovative rehabilitation treatments based on these findings.

Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer's disease.

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer's disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

Effects of Pharmacological Treatments in Alzheimer's Disease: Permutation Entropy-Based EEG Complexity Study.

Alzheimer's disease (AD) is a neurodegenerative brain disease affecting cognitive and physical functioning. The currently available pharmacological treatments for AD mainly contain cholinesterase inhibitors (AChE-I) and N-methyl-D-aspartic acid (NMDA) receptor antagonists (i.e., memantine). Because brain signals have complex nonlinear dynamics, there has been an increase in interest in researching complexity changes in the time series of brain signals in individuals with AD. In this study, we explore the electroencephalographic (EEG) complexity for making better observation of pharmacological therapy-based treatment effects on AD patients using the permutation entropy (PE) method. We examined EEG sub-band (delta, theta, alpha, beta, and gamma) complexity in de-novo, monotherapy (AChE-I), dual therapy (AChE-I and memantine) receiving AD participants compared with healthy elderly controls. We showed that each frequency band depicts its own complexity profile, which is regionally altered between groups. These alterations were also found to be associated with global cognitive scores. Overall, our findings indicate that entropy measures could be useful to show medication effects in AD.

Resting State Alpha Electroencephalographic Rhythms Are Affected by Sex in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment: A Retrospective and Exploratory Study.

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aß42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.

Association between executive and physical functions in people with Parkinson's disease.

PURPOSE: People with Parkinson's disease (PD) can develop cognitive and physical impairments. There is limited evidence on the association between executive function and physical function in people with PD. OBJECTIVE: We aimed to investigate the association between the executive and physical functions in people with Parkinson's disease (PD) by comparing healthy controls. METHOD: Thirty-three patients diagnosed with PD and 33 healthy controls were included in the study. PD group was divided into two subgroups according to their scores on executive tests as high performers (PD-HPs; n = 17) and low performers (PD-LPs; n = 16). The severity of motor symptoms disease severity, executive function, global cognitive function, reaction time, hand function, functional capacity, physical activity, and balance confidence was assessed by the validated instruments. RESULTS: The PD group had less physical function and executive function compared to healthy controls (p < 0.05). The PD-LPs group had less physical and cognitive function than the PD-HPs group (p < 0.05). The executive functions were significantly correlated with almost all variables in both people with PD and healthy people, and correlations were moderate to strong (p < 0.05). However, the correlation coefficients were relatively higher in people with PD compared to healthy controls. CONCLUSION: There was a significant association between executive and physical function in people with PD. Future studies should be conducted to determine whether the treatment of one of these dysfunctions affects the other.

Telehealth applications used for self-efficacy levels of family caregivers for individuals with dementia: A systematic review and Meta-analysis.

BACKGROUND: The effectiveness of telehealth applications for family caregivers of individuals with dementia remains unclear. The aim of this study is to investigate how telehealth-based interventions applied for family caregivers of individuals with dementia affect their self-efficacy levels, caregiving burden, stress, depression, and quality of life. MATERIALS AND METHODS: This was a systematic review. Screening took place between April 30 and May 5, 2022, for the scope of the past 10 years (January 2012/May 2022). The related studies were screened over ten (10) databases and search engines both in English and Turkish, including CINAHL, Cochrane Library, MEDLINE, PsycINFO, PubMed and Web of Science, ULAKBIM, Turkish Medline, Türkiye Klinikleri, and YOK National Thesis Center. Keywords included in various medical topic titles identified upon consultation with literature review experts from a library. Methodological quality of the studies was evaluated using Critical Appraisal Checklists developed by the Joanna Briggs Institute for experimental and quasi-experimental studies. The data were synthesized by meta-analysis. RESULTS: Two hundred and twelve (212) records were accessed in the databases. Of that, 12 studies (covering 1,013 caregivers) were selected for the meta-analysis. Statistically, the self-efficacy mean score was significantly higher in the intervention group than the control group after the intervention (SMD: 1.08, Z= 3.12, p= 0.002). The effectiveness of telehealth-based applications for caregivers' caregiving burden, stress, depression and quality of life -- except for self-efficacy - was evaluated. The results of the intervention and control groups were similar after the intervention (SMD: -0.17, Z= 0.82, p= 0.41; MD: -0.60, Z= 0.49, p= 0.63, SMD: -0.04, Z= 0.13, p= 0.98; SMD: 0.15, Z= 0.47, p= 0.64, respectively). CONCLUSIONS: This systematic review and meta-analysis showed that telehealth applications were effective in elevating the self-efficacy levels of caregivers of individuals with dementia. However, no statistically significant difference was observed in terms of caregiving burden, stress, depression, or quality of life for caregivers.

Structural and Functional Changes in Mild Cognitive Impairment in Parkinson's Disease.

Background and Objectives: The pathophysiology of mild cognitive impairment in Parkinson's disease (PD-MCI) is still not fully elucidated. It has been shown in a few studies in the literature that volume loss in the occipital, parietal and frontal cortices and atrophy in the hippocampus of PD-MCI patients can occur in the early stages of PD. The aim of this study was to evaluate the relationship between gray and white matter volumes and different neuropsychological tests and volumetric magnetic resonance imaging parameters in patients with mild cognitive impairment in Parkinson's disease (PD-MCI). Materials and Methods: Twenty-six PD-MCI and twenty-six healthy elderly (HC) were included in this study. Results: We found that Mini Mental State Examination, Trail Making Test Part A, Clock Drawing Test, Benton Line Judgment Orientation Test and pentagon figure-copying scores were impaired in PD-MCI patients due to the decrease in brain volumes. Conclusions: Our study revealed that among PD-MCI patients, there was a more noticeable decline in White matter volume (WMV) based on volumetric Magnetic Resonance Imaging (MRI) compared to the localized loss of GMV. We think that these abnormal neuropsychological tests in PD-MCI patients can be used as pretests in the evaluation of the stage of transition to dementia.

Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Taxonomically-related Word Pairs Evoke both N400 and LPC at Long SOA in Turkish.

Semantic priming in Turkish was examined in 36 right-handed healthy participants in a delayed lexical decision task via taxonomic relations using EEG. Prime-target relations included related- unrelated- and pseudo-words. Taxonomically related words at long stimulus onset asynchrony (SOA) were shown to modulate N400 and late positive component (LPC) amplitudes. N400 semantic priming effect in the time window of 300-500 ms was the largest for pseudo-words, intermediate for semantically-unrelated targets, and smallest for semantically-related targets as a reflection of lexical-semantic retrieval. This finding contributes to the ERP literature showing how remarkably universal the N400 brain potential is, with similar effects across languages and orthography. The ERP data also revealed different influences of related, unrelated, and pseudo-word conditions on the amplitude of the LPC. Attention scores and mean LPC amplitudes of related words in parietal region showed a moderate correlation, indicating LPC may be related to "relationship-detection process".

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.

Investigation of the Factors Affecting Quality of Life in Patients with Mild to Moderate Alzheimer's Disease in Terms of Patients and Caregivers.

Background and Objectives: As with other chronic diseases with limited medical treatment, the most important goal of Alzheimer's disease (AD) treatment is to provide a better quality of life (QoL). The purpose of this study was to investigate the factors affecting the QoL of patients with mild to moderate AD in terms of patients and caregivers. Materials and Methods: Seventy-three home-dwelling patients with AD and their caregivers participated in this prospective, cross-sectional study. The patients were asked about their cognition, depression and a self-rating part of a QoL questionnaire. The caregivers were asked about their patients' sociodemographic information, sleepiness, activities of daily living and a proxy rating part of a QoL questionnaire. Results: The self-rated QoL was higher than that provided by the proxy rating. Cognition (p = 0.02), sleepiness (p < 0.01) and depression (p = 0.03) were correlated with the self-rated QoL, while the patient's independence level in activities of daily living was correlated with the proxy-rated QoL (p < 0.05). In regard to predicting QoL according to linear regression analysis, the following were statistically significant: depression was for total score, depression and cognition were for the self-rating and instrumental activities of daily living was for the proxy rating (p < 0.01). Conclusions: While individual factors such as psychology are an important determinant of QoL for patients with AD, objective conditions such as the independence of the patient in daily life are important for the caregiver. While evaluating the quality of life of AD patients, it is important to remember that patients and caregivers have different priorities, and the priorities of both should be taken into account when planning a treatment program.

Adult Spinal Primary Leptomeningeal Medulloblastoma Presenting as Pseudotumour Cerebri Syndrome.

A previously well 34-year-old man presented with severe pseudotumour cerebri. Imaging showed that he had a cauda equina tumour which proved to be a medulloblastoma. There was no tumour mass in the posterior fossa so we assume that this was a primary leptomeningeal medulloblastoma. In patients with somewhat atypical pseudotumour, spinal imaging should always be considered.

The effects of support groups on dementia caregivers: A mixed method study.

The aim of this qualitative and quantitative study was to understand the effects of support group interventions on the caregiving burden of individuals providing care for people with dementia. This study used the Caregiver Burden Inventory, and focus group interviews (18 caregivers), which were conducted using a semi-structured interview form. The initial study sample was 37 primary caregivers; however, the final analysis included 30 caregivers. The quantitative data were analyzed by paired sample t-test. The interviews being analyzed using content analysis. It was found that there was a significant decrease in the scores for total burden (p = 0.049), social burden (p = 0.008) and emotional burden (p = 0.000) after the intervention. The content analyze revealed three main themes ("having knowledge," "calming down," and "acceptance"). Overall, it was concluded that support groups are effective in reducing caregiver burden.

Meta-Analysis of Social Cognition in Mild Cognitive Impairment.

Social cognitive abilities are impaired in Alzheimer disease and other dementias. Recent studies suggested that social cognitive abilities might be also impaired in mild cognitive impairment (MCI). Current meta-analysis aimed to summarize available evidence for deficits in theory of mind (ToM) and emotion recognition in MCI. In this meta-analysis of 17 studies, facial emotion recognition and ToM performances of 513 individuals with MCI and 693 healthy controls were compared. Mild cognitive impairment was associated with significant impairments falling in the medium effect sizes range in ToM ( d = 0.63) and facial emotion recognition ( d = 0.58). Among individual emotions, recognition of fear and sadness were particularly impaired. There were no significant between-group differences in recognition of disgust, happiness, and surprise. Social cognitive deficits were more severe in multidomain MCI. There is a need for longitudinal studies investigating the potential role of social cognitive impairment in predicting conversion to dementia.

Effects of donepezil on liver and kidney functions for the treatment of Alzheimer's disease.

Aim of the present study is to investigate the effects of medication with donepezil (acetylcholinesterase inhibitor) on the liver and kidney function in Alzheimer's disease (AD) and to compare the effects of donepezil medication during short (one month) and long term (six years) follow-ups. We evaluated female and male patients from Cukurova [42 AD patients; short term (5 mg/day)] and Dokuz Eylul [68 AD patients; long term (10 mg/day)] University Hospital. The results compared with the geriatric population without dementia in other words who are not in medication with donepezil. For short term evaluation all subjects underwent periodic examination with tests regarding hepatic and renal functions; firstly, before starting treatment and then repeated one month later. For long term evaluation all subjects underwent periodic examination with tests regarding hepatic and renal functions; three times at the end of each two consecutive years of treatment with donepezil. AD patients' results were also compared with 79 neurologically healthy geriatric patients without dementia who were over 65 years of age and were not receiving medication with donepezil. For this task, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are used to predict possible liver damage, while the blood urea nitrogen (BUN) and creatinine (CRE) levels for kidney damage. No significant difference between the groups regarding the routine control of biochemical parameters was observed in short term drug medication. In long term patients' group; the effects of two years use of donepezil on renal and hepatic function were also evaluated and levels of AST, ALT, BUN and CRE were found to be increased significantly compared to pretreatment levels. But, they remained in the reference intervals. However, levels of AST and ALT at the end of the fourth year of therapy were similar to those measured at the end of the second year, levels of BUN and CRE continuing to increase with staying below the reference limits. Functional markers obtained at the end of the sixth year of therapy were not differing from those of the fourth year. No significant difference was found during comparisons within the results of the neurologically healthy geriatric patient group. During comparisons between the two groups, measurements obtained at all-time points were significantly high in donepezil treated AD patients. We concluded that customized dosage according to hepatic and renal functions is necessary for using acetylcholinesterase inhibitor in AD patients.

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.