Is Hippocampal Volume a Relevant Early Marker of Dementia?

OBJECTIVE: Hippocampal volume (HV) is a key imaging marker to improve Alzheimer's disease risk prediction. However, longitudinal studies are rare, and hippocampus may also be implicated in the subtle aging-related cognitive decline observed in dementia-free individuals. Our aim was to determine whether HV, measured by manual or automatic segmentation, is associated with dementia risk and cognitive decline in participants with and without incident dementia. METHODS: At baseline, 510 dementia-free participants from the French longitudinal ESPRIT cohort underwent magnetic resonance imaging. HV was measured by manual and by automatic segmentation (FreeSurfer 6.0). The presence of dementia and cognitive functions were investigated at each follow-up (2, 4, 7, 10, 12, and 15 years). Cox proportional hazards models and linear mixed models were used to assess the association of HV with dementia risk and with cognitive decline, respectively. RESULTS: During the 15-years follow-up, 42 participants developed dementia. Reduced HV (regardless of the measurement method) was significantly associated with higher dementia risk and cognitive decline in the whole sample. However, only the automatically measured HV was associated with cognitive decline in dementia-free participants. CONCLUSION: These results suggest that HV can be used to predict the long-term risk of dementia but also cognitive decline in a dementia-free population. This raises the question of the relevance of HV measurement as an early marker of dementia in the general population.

Late-life cynical hostility is associated with white matter alterations and the risk of Alzheimer's disease.

BACKGROUND: Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD. METHODS: In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA. RESULTS: Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10-6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10-4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes. CONCLUSIONS: High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.

Lifetime major depression and grey-matter volume

Background: There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS). Methods: We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities. Results: Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype. Limitations: This study was limited by its cross-sectional design. Conclusion: Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.

Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.

OBJECTIVES: Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. RESULTS: The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.

Ambient Air Pollution Exposure and Cerebral White Matter Hyperintensities in Older Adults: A Cross-Sectional Analysis in the Three-City Montpellier Study.

BACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on vascular health. OBJECTIVE: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH). METHODS: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes. RESULTS: Participants' (n=582) median age at MRI was 70.7 years [interquartile range (IQR): 6.1], and 52% (n=300) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) µg/m3 for PM2.5, 48.9 (14.6) µg/m3 for NO2, and 2.66 (0.60) 10-5/m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden [odds ratio (OR) for an IQR increase=1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile]. Associations for other regional WMH volumes were inconsistent. CONCLUSION: In this population-based study in older adults, PM2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution. https://doi.org/10.1289/EHP12231.

Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia.

BACKGROUND: Glucometabolic changes, such as high glycemic load (GL) diet and insulin resistance (IR), are potential risk factor of Alzheimer's disease (AD). Yet, the effect of these factors on brain alterations that contribute to AD pathology has not been clearly demonstrated. OBJECTIVE: We aimed to assess the relationship of GL and IR with gray matter volumes involved in prodromal dementia. METHODS: GL and Triglyceride-Glucose (TyG) index, an IR surrogate marker, were calculated in 497 participants who underwent magnetic resonance imaging (MRI). The gray matter volumes most related to prodromal dementia/mild cognitive impairment (diagnosed in 18/158 participants during the 7-year follow-up) were identified using a data-driven machine learning algorithm. RESULTS: Higher GL diet was associated with reduced amygdala volume. The TyG index was negatively associated with the hippocampus, amygdala, and putamen volumes. CONCLUSION: These results suggest that GL and IR are associated with lower gray matter volumes in brain regions involved in AD pathology.

Structural brain alterations in older adults exposed to early-life adversity.

BACKGROUND: Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype. METHOD: Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies. RESULTS: Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically. CONCLUSIONS: Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.

Structural brain changes with lifetime trauma and re-experiencing symptoms is 5-HTTLPR genotype-dependent.

Background: Findings on structural brain alterations following trauma are inconsistent due probably to heterogeneity in imaging studies and population, clinical presentations, genetic vulnerability, and selection of controls. This study examines whether trauma and re-experiencing symptoms are associated with specific alterations in grey matter volumes and if this varies according to 5-HTTLPR genotype. Methods: Structural MRI was used to acquire anatomical scans from 377 community-dwelling older adults. Quantitative regional estimates of 22 subregional volumes were derived using FreeSurfer software. Lifetime trauma was assessed using the validated Watson's PTSD inventory, which evaluates the most severe trauma experienced according to DSM criteria. Analyses adjusted for age, sex, total brain volume, head injury, and comorbidities. Results: Of the 212 participants reporting lifetime trauma, 35.4% reported re-experiencing symptoms and for 1.9%, this was severe enough to meet criteria for full threshold PTSD. In participants with the SS 5-HTTLPR genotype only, re-experiencing symptoms were associated with smaller volumes in middle and superior temporal, frontal (lateral orbital, rostral and caudal middle) and parietal (precuneus, inferior and superior) regions. The trauma-exposed participants without re-experiencing symptoms were not significantly different from the non-trauma-exposed participants except for smaller precuneus and superior parietal region in traumatized participants and a larger amygdala in traumatized women specifically. Conclusions: In the non-clinical sample, lifetime trauma and re-experiencing symptoms were associated with smaller volume in prefrontal, temporal and parietal cortex subregions, and this varied according to serotonergic genetic vulnerability, 5-HTTLPR SS individuals being most susceptible.

Antecedentes: Los hallazgos sobre las alteraciones estructurales cerebrales luego del trauma son inconsistentes debido probablemente a heterogeneidad en los estudios de imagen y población, presentaciones clínicas, vulnerabilidad genética y selección de los controles. Este estudio examina si el trauma y los síntomas de reexperimentación están asociados con alteraciones específicas en los volúmenes de materia gris y si esto varía de acuerdo al genotipo 5-HTTLPR.Métodos: Se utilizó IMR estructural para adquirir mapeos anatómicos de 377 adultos mayores residentes en viviendas comunitarias. Se derivaron estimados regionales cuantitativos de 22 volúmenes sub-regionales usando el software FreeSurfer. Se evaluó trauma a través de la vida utilizando el inventario para TEPT validado de Watson, que evalúa el trauma más severo experimentado de acuerdo a criterios DSM. Se ajustaron los análisis por edad, sexo, volumen cerebral total, trauma encefálico y comorbilidades.Resultados: De los 212 participantes que reportaron trauma en la vida, un 35.4% reportó síntomas de reexperimentación y para el 1,9% fueron lo suficientemente severos para cumplir los criterios para el umbral completo del TEPT. Sólo en los participantes con el genotipo SS 5-HTTLPR, los síntomas de reexperimentación se asociaron con menores volúmenes en las regiones temporal media y superior, frontal (orbitolateral, rostral y caudal medial) y parietal (precúneo, inferior y superior). Los participantes expuestos a trauma sin síntomas de reexperimentación no variaron significativamente respecto a los no expuestos a trauma excepto por menor tamaño del precúneo y región superior parietal en los participantes traumatizados y un mayor tamaño de la amígdala específicamente en mujeres traumatizadas.Conclusiones: En una muestra no-clínica, el trauma a través de la vida y los síntomas de reexperimentación se asociaron con menor tamaño en sub-regiones corticales prefrontales, temporales y parietales, y esto varía de acuerdo a la vulnerabilidad genética serotoninérgica, siendo más susceptibles los individuos 5-HTTLPR SS.

Hippocampal shape analysis for Alzheimer's disease using an efficient hypothesis test and regularized discriminative deformation.

In this article, we present a framework to perform statistical shape analysis for segmented hippocampi, including an efficient permutation test for detecting subtle class differences, and a regularized discriminative direction method for visualizing the shape discrepancy. Fisher permutation and bootstrap tests are preferred to traditional hypothesis tests which impose assumptions on the distribution of the samples. In this article, an efficient algorithm is adopted to rapidly perform the exact tests. We extend this algorithm to multivariate data by projecting the shape descriptors onto an informative direction that preserves the original discriminative information as much as possible to generate a scalar test statistic. This informative direction is further used to seek a discriminative direction to isolate the discriminative shape difference between classes from the individual variability. Compared with existing methods, the discriminative direction used in this article is regularized by requiring that the shapes deformed along it respect the underlying shape distribution as well as reflecting the essential shape differences between two populations. Hence, a more accurate localization of difference is produced. We apply our methods to analyze the hippocampal shapes for controls and subjects with Alzheimer's disease from the publicly available OASIS MRI database. We show how to localize the shape differences between the two classes.

Risk factors of transition from normal cognition to mild cognitive disorder: the PATH through Life Study.

AIMS: The aim of this study was to identify physical and mental health and lifestyle predictors of transition from normal cognition to mild cognitive disorder (MCD). METHODS: A total of 2,082 individuals, aged 60-64 years, were assessed at 2 time-points 4 years apart for mild cognitive impairment (MCI) and other MCDs. RESULTS: The main predictors of conversion to MCI and to other mild cognitive disorders were past alcohol intake, current anxiety and depression medication, increased systolic blood pressure, and past smoking. CONCLUSION: Participants with a history of smoking or harmful alcohol consumption, hypertension, or who took medication for anxiety or depression were at increased risk of transitioning to MCI or any MCD. Strategies targeted at managing the above risk factors may have benefits in preventing mild cognitive decline in relatively healthy middle-aged individuals living in the community.

Increased Serum C-reactive Protein and Corpus Callosum Alterations in Older Adults.

Chronic systemic low-grade inflammation is associated with aging, but little is known on whether age-related inflammation affects brain structure, particularly white matter. The current study tested the hypothesis that in older adults without dementia, higher serum levels of high-sensitivity C-reactive protein (hs-CRP) are associated with reduced corpus callosum (CC) areas. French community-dwelling subjects (ESPRIT study) aged 65 and older (N=101) underwent hs-CRP testing and structural magnetic resonance imaging (MRI). Multiple linear regression models were carried out. In the unadjusted model, higher hs-CRP level was significantly associated with smaller anterior, mid, and total midsagittal CC areas, but not with the posterior CC area. These associations were independent of demographic characteristics and intracranial volume. After adjustment for body mass index, diabetes, inflammation-related chronic pathologies and white matter lesions (WML), only the associations between hs-CRP level and smaller anterior and total midsagittal CC areas were still significant, although weaker. These findings suggest that low-grade inflammation is associated with CC structural integrity alterations in older adults independently of physical or neuropsychiatric pathologies.

Total and regional gray matter volume is not related to APOE*E4 status in a community sample of middle-aged individuals.

BACKGROUND: The APOE*E4 allele has been associated with greater gray matter atrophy and with Alzheimer's disease. The aim of this study was to investigate whether the relationship between cerebral gray matter atrophy and APOE*E4 genotype was also present in a community-dwelling, nondemented 60- to 64-year-old cohort. METHODS: Hippocampal and amygdalar volumes were manually traced and analyzed on 331 cranial T1-weighted magnetic resonance imaging (MRI) scans to detect differences associated with APOE*E4 genotype. Voxel-based morphometric (VBM) analyses were applied to detect regional gray matter volume differences. RESULTS: No total, hippocampal, or amygdalar gray matter volume difference was detected between APOE*E4 carriers and noncarriers. CONCLUSIONS: In nondemented 60- to 64-year-olds, there was no association between APOE genotype and gray matter volume using both region-of-interest analysis and VBM.

Follow-up of mild cognitive impairment and related disorders over four years in adults in their sixties: the PATH Through Life Study.

AIMS: The study aimed to estimate incidence rates of mild cognitive impairment and related disorders, and conversion to dementia. METHODS: The data are drawn from the PATH Through Life Study. Baseline assessment in 2001-2002 included 2,551 participants 60-64 years old with 2,222 participating in a 4-year follow-up. Those screened positive with a cognitive assessment received clinical assessment for diagnoses of mild cognitive disorders (MCD) or dementia using established clinical criteria. Prevalence and incidence rates for the cohort were estimated with predictive regression models. RESULTS: Annual incidence of dementia was 0.25%. Prevalence of mild cognitive impairment was 4.2%, age-associated memory impairment was 2.4%, age-associated cognitive decline was 7.6%, mild neurocognitive disorders occurred in 12.9% and other cognitive disorders in 7.3%. Prevalence of any diagnosis of any MCD (Any-MCD) was 29.5% and the annual incidence rate for Any-MCD was 5.7%. Agreement for specific diagnoses between waves 1 and 2 was fair to poor (0-47.0%), but agreement for Any-MCD over 4 years was 89.0%. CONCLUSION: MCD diagnoses do not predict dementia at a 4-year follow-up in young-old adults. Prevalence rates for MCD vary greatly depending on the criteria and time of assessment.

Repatriation is associated with isthmus cingulate cortex reduction in community-dwelling elderly.

OBJECTIVES: The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly its long-term neural consequences. We tested the hypothesis that a serious SLE (repatriation of French citizens living in Algeria in 1962) is associated with changes in brain regions previously implicated in psychopathology (hippocampus, amygdala, corpus callosum, prefrontal cortex, anterior, posterior and isthmus cingulate cortex (ICC)) in a large elderly population. METHODS: Structural magnetic resonance imaging was used to acquire anatomical scans from 82 subjects repatriated from Algeria and 339 subjects without this experience or any other trauma. We derived quantitative regional estimates of subcortical volume using FreeSurfer Software. The General Linear Model was used to test the association between repatriation and changes in brain volume adjusted for confounders (gender, age, education, total brain volume, traumatic brain injury, Mini Mental State Examination score at baseline, current and lifetime major depression and recent SLEs). RESULTS: Repatriation to France was associated with reduced volume in a number of areas; however, only left and right ICC survived to false discovery rate correction. CONCLUSIONS: In the elderly a previous (approximately 40 years before) serious SLE could be associated with long-term volume reduction in the ICC, independently of psychopathology.

Smaller hippocampal volume in current but not in past depression in comparison to healthy controls: Minor evidence from an older adults sample.

BACKGROUND: Structural neuroimaging studies revealed a consistent pattern of volumetric reductions in both hippocampus (HC) and anterior cingulate cortex (ACC) of individuals with major depressive episode(s) (MDE). This study investigated HC and ACC volume differences in currently depressed individuals (n = 150), individuals with a past lifetime MDE history (n = 79) and healthy controls (n = 287). METHODS: Non-demented individuals were recruited from a cohort of community-dwelling older adults (ESPRIT study). T1-weighted magnetic resonance images and FreeSurfer Software (automated method) were used. Concerning HC, a manual method of measurement dividing HC into head, body, and tail was also used. General Linear Model was applied adjusting for covariates. RESULTS: Current depression was associated with lower left posterior HC volume, using manual measurement, in comparison to healthy status. However, when we slightly changed sub-group inclusion criteria, results did not survive to correction for multiple comparisons. CONCLUSIONS: The finding of lower left posterior HC volume in currently depressed individuals but not in those with a past MDE compared to healthy controls could be related to brain neuroplasticity. Additionally, our results may suggest manual measures to be more sensitive than automated methods.

Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample.

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative sample (n=432) and a sample with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. Samples did not differ in CC area or intra-cranial volume. In the normative sample, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-individual RT variability. In the mild cognitive disorders sample, SRT, CRT and intra-individual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the sample with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative sample. There were no associations with APOE genotype. We conclude that intra-individual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.

Hippocampus and amygdala volumes in a random community-based sample of 60-64 year olds and their relationship to cognition.

Reduced volumes of the hippocampus (HC) and amygdala (AG) are potential biomarkers for Alzheimer's disease (AD) and other neuropsychiatric disorders. Published studies on HC and AG volumes suffer from methodological limitations, and a valid and reliable normative database does not exist. This study aimed to establish a database of HC and AG volumes from a large community sample of participants 60-64 years old and relate them to cognition. A total of 452 randomly selected participants (from 622 approached) were retained in the study (238 males, 214 females), and all received brain MRI scans, as well as cognitive and physical assessments. HC and AG volumes were estimated from manual tracings on T1-weighted images, and intracranial volume (ICV) was obtained from an automated program. In both sexes, right hippocampi were larger than left, while left amygdala were larger than right. The only correlation to remain significant after normalization was left HC volume and percent retention of a word list in females. This study provides a HC and AG volumetrics database and describes its relationship with cognitive performance in a representative sample using a standard methodology that will be a reference for future studies. It will therefore have clinical applicability in early AD and other disorders.

Evaluation of a research diagnostic algorithm for DSM-5 neurocognitive disorders in a population-based cohort of older adults.

BACKGROUND: There is little information on the application and impact of revised criteria for diagnosing dementia and mild cognitive impairment (MCI), now termed major and mild neurocognitive disorders (NCDs) in the DSM-5. We evaluate a psychometric algorithm for diagnosing DSM-5 NCDs in a community-dwelling sample, and characterize the neuropsychological and functional profile of expert-diagnosed DSM-5 NCDs relative to DSM-IV dementia and International Working Group criteria for MCI. METHODS: A population-based sample of 1644 adults aged 72-78 years was assessed. Algorithmic diagnostic criteria used detailed neuropsychological data, medical history, longitudinal cognitive performance, and informant interview. Those meeting all criteria for at least one diagnosis had data reviewed by a neurologist (expert diagnosis) who achieved consensus with a psychiatrist for complex cases. RESULTS: The algorithm accurately classified DSM-5 major NCD (area under the curve (AUC) = 0.95, 95% confidence interval (CI) 0.92-0.97), DSM-IV dementia (AUC = 0.91, 95% CI 0.85-0.97), DSM-5 mild NCD (AUC = 0.75, 95% CI 0.70-0.80), and MCI (AUC = 0.76, 95% CI 0.72-0.81) when compared to expert diagnosis. Expert diagnosis of dementia using DSM-5 criteria overlapped with 90% of DSM-IV dementia cases, but resulted in a 127% increase in diagnosis relative to DSM-IV. Additional cases had less severe memory, language impairment, and instrumental activities of daily living (IADL) impairments compared to cases meeting DSM-IV criteria for dementia. DSM-5 mild NCD overlapped with 83% of MCI cases and resulted in a 19% increase in diagnosis. These additional cases had a subtly different neurocognitive profile to MCI cases, including poorer social cognition. CONCLUSION: DSM-5 NCD criteria can be operationalized in a psychometric algorithm in a population setting. Expert diagnosis using DSM-5 NCD criteria captured most cases with DSM-IV dementia and MCI in our sample, but included many additional cases suggesting that DSM-5 criteria are broader in their categorization.

Weekly alcohol consumption, brain atrophy, and white matter hyperintensities in a community-based sample aged 60 to 64 years.

OBJECTIVE: The objective of this study was to determine the association between weekly alcohol consumption and brain atrophy in adults aged 60 to 64 years. METHODS: Brain magnetic resonance imaging scans from 385 adults recruited through a community survey were analyzed. Automated segmentation and manual tracing methods were used to obtain brain subvolumes and automated methods were used to obtain quantification and localization of white matter hyperintensities. Visual measures of cortical atrophy were obtained as were data on health and lifestyle factors. Alcohol consumption was assessed with the Alcohol Use Disorders Identification Test. RESULTS: In men, weekly alcohol consumption had a positive linear association with ventricular volume and gray matter and a negative linear association with white matter. In women, weekly alcohol consumption had a nonlinear relationship with cerebrospinal fluid and white matter. Alcohol consumption was not associated with white matter hyperintensities, corpus callosum size, hippocampal or amygdala volumes in analyses adjusting for confounding variables. CONCLUSION: An association between alcohol consumption and brain atrophy is evident at the population level. In women, detrimental effects of alcohol on the brain appear to occur at lower levels of consumption. It remains possible that low levels of alcohol consumption have neuroprotective benefits but is clear that high levels of consumption are detrimental.