Cognitive Aspects of COVID-19.

PURPOSE OF REVIEW: Since the beginning of the coronavirus disease 2019 pandemic, many lasting neurological sequelae including cognitive impairment have been recognized as part of the so-called long COVID syndrome. This narrative review summarizes the cognitive aspects of COVID-19. RECENT FINDINGS: Studies have consistently identified attention, memory, and executive functions as the cognitive domains most often affected by COVID-19 infection. Many studies have also reported neuroimaging, biofluid, and neurophysiological abnormalities that could potentially reflect the pathophysiological aspects of post-COVID cognitive impairment. While patients suffering from dementia have an elevated risk of COVID-19 infection, increasing evidence has also indicated that COVID-19 infection may increase the risks of Alzheimer's disease, suggesting bidirectional relationships. Post-COVID cognitive dysfunction is a pervasive and multifaceted problem and we are surely in our infancy of understanding. Future elucidation into the long-term effects, mechanisms, and therapies will depend on a concerted effort from clinicians, researchers, patients, and policy-makers alike.

Variably Protease-sensitive Prionopathy in a Middle-aged Man With Rapidly Progressive Dementia.

Variably protease-sensitive prionopathy (VPSPr) is a recently described sporadic prion disease with distinctive clinical and histopathological features. We report the clinical, imaging, and neuropathological features of VPSPr in a 46-year-old right-handed man who presented with progressive cognitive decline, behavior disturbances, and a 50-pound weight loss over 6 months. The initial evaluation revealed severe cognitive impairment with no focal neurologic deficits. His cognitive, psychiatric, and behavior symptoms progressed rapidly, and he died 12 months after the initial visit. Throughout his disease course, workup for rapid progressive dementia was unremarkable except that brain MRI diffusion-weighted imaging showed persistent diffuse cortical and thalamic signal abnormalities. Sporadic Creutzfeldt-Jakob disease was highly suspected; however, two EEGs (8 months apart) demonstrated only nonspecific cerebral dysfunction. The patient's CSF 14-3-3 protein was negative at the initial visit and again 8 months later. His CSF real-time quaking-induced conversion and total tau level were normal. An autopsy of his brain was performed, and the neuropathological findings confirmed VPSPr. Our case underlines the importance of considering VPSPr in the spectrum of prion disease phenotypes when evaluating individuals with rapidly progressive dementia.

Differences in [123I]Ioflupane Striatal Binding Between African American and White Patients.

Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore whether differences exist in [123I]ioflupane binding, which reflects dopamine transporter binding, between African American and White individuals. Methods: Medical charts were reviewed for patients who underwent [123I]ioflupane SPECT imaging as part of routine practice in a single academic medical center. All images were visually graded as showing normal or abnormal presynaptic dopaminergic function (normal or abnormal scan status). Quantitative [123I]ioflupane uptake as measured by the specific binding ratios in the right and left striata and their subregions (caudate nucleus and anterior and posterior putamen) and by bilateral putamen-to-caudate ratios were compared between African American and White patients using multiple linear regression adjusted for age, sex, and abnormal scan status. Additional models included an ethnicity-by-abnormal-scan-status interaction term to determine whether abnormal scan status was modulated by ethnicity effect. Results: The percentage of patients with abnormal scan status was comparable between African American and White patients. Compared with White patients (n = 173), African American patients (n = 82) had statistically significantly higher uptake as measured by specific binding ratios in the right and left striata and some of their subregions (right and left caudate nuclei and right posterior putamen). Ethnicity-by-abnormal-scan-status interactions were not statistically supported for any models. Conclusion: We observed differences in [123I]ioflupane binding between African American and White patients independent of presynaptic dopaminergic dysfunction status. Future studies are needed to examine whether and how ethnicity affects dopamine transporter binding activities and its clinical relevance.

Posttraumatic Epilepsy and Dementia Risk.

Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes. Objective: To investigate associations of PTE with dementia risk. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years. Data were analyzed between March 14, 2023, and January 2, 2024. The study took place in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC study participants initially enrolled, 2061 were ineligible and 1173 were excluded for missing data, resulting in 12 558 included participants. Exposures: Head injury was defined by self-report and International Classification of Diseases (ICD) diagnostic codes. Seizure/epilepsy was defined using ICD codes. PTE was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after head injury. Head injury, seizure/epilepsy, and PTE were analyzed as time-varying exposures. Main Outcomes and Measures: Dementia was defined using cognitive assessments, informant interviews, and ICD and death certificate codes. Adjusted Cox and Fine and Gray proportional hazards models were used to estimate dementia risk. Results: Participants had a mean (SD) age of 54.3 (5.8) years at baseline, 57.7% were female, 28.2% were of self-reported Black race, 14.4% were ultimately categorized as having head injury, 5.1% as having seizure/epilepsy, and 1.2% as having PTE. Over a median follow-up of 25 (25th to 75th percentile, 17-30) years, 19.9% developed dementia. In fully adjusted models, compared with no head injury and no seizure/epilepsy, PTE was associated with 4.56 (95% CI, 4.49-5.95) times the risk of dementia, while seizure/epilepsy was associated with 2.61 (95% CI, 2.21-3.07) times the risk and head injury with 1.63 (95% CI, 1.47-1.80) times the risk. The risk of dementia associated with PTE was significantly higher than the risk associated with head injury alone and with nontraumatic seizure/epilepsy alone. Results were slightly attenuated in models accounting for the competing risks of mortality and stroke, but patterns of association remained similar. In secondary analyses, the increased dementia risk associated with PTE occurring after first vs second head injury and after mild vs moderate/severe injury was similar. Conclusions and Relevance: In this community-based cohort, there was an increased risk of dementia associated with PTE that was significantly higher than the risk associated with head injury or seizure/epilepsy alone. These findings provide evidence that PTE is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury.

Association between structural brain MRI abnormalities and epilepsy in older adults.

OBJECTIVE: To determine the association between brain MRI abnormalities and incident epilepsy in older adults. METHODS: Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. RESULTS: Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3). INTERPRETATION: This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.

Association of Olfaction and Microstructural Integrity of Brain Tissue in Community-Dwelling Adults: Atherosclerosis Risk in Communities Neurocognitive Study.

BACKGROUND AND OBJECTIVES: Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. METHODS: Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. RESULTS: Among 1,418 participants (mean age 76 ± 5 years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9 ± 2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely the hippocampus (ß -0.79 [95% CI -0.94 to -0.65] units lower olfaction score per 1 SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared with those with normal cognition (e.g., ßhippocampus -0.75 [95% CI -1.02 to -0.49] and -0.44 [95% CI -0.63 to -0.26] for MCI and normal cognition, respectively, p interaction = 0.004). DISCUSSION: Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with those with MCI may reflect the earlier vs later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.

Association of Head Injury With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Cohort.

BACKGROUND AND OBJECTIVES: Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals. Head injury is also a risk factor for acquired epilepsy, but the degree to which prior head injury may contribute to LOE is less well understood. Our objective was to determine the association between head injury and subsequent development of LOE. METHODS: Included were 8,872 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study with continuous Centers for Medicare Services fee-for-service (FFS) coverage (55.1% women, 21.6% Black). We identified head injuries through 2018 from linked Medicare fee for service claims for inpatient/emergency department care, active surveillance of hospitalizations, and participant self-report. LOE cases through 2018 were identified from linked Medicare FFS claims. We used Cox proportional hazards models to evaluate associations of head injury with LOE, adjusting for demographic, cardiovascular, and lifestyle factors. RESULTS: The adjusted hazard ratio (HR) for developing LOE after a history of head injury was 1.88 (95% confidence interval [CI] 1.44-2.43). There was evidence for dose-response associations with greater risk for LOE with increasing number of prior head injuries (HR 1.37, 95% CI 1.01-1.88 for 1 prior head injury and HR 3.55, 95% CI 2.51-5.02 for 2+ prior head injuries, compared to no head injuries) and with more severe head injury (HR 2.53, 95% CI 1.83-3.49 for mild injury and HR 4.90, 95% CI 3.15-7.64 for moderate/severe injury, compared to no head injuries). Associations with LOE were significant for head injuries sustained at older age (age ≥67 years: HR 4.01, 95% CI 2.91-5.54), but not for head injuries sustained at younger age (age < 67 years: HR 0.98, 95% CI 0.68-1.41). DISCUSSION: Head injury was associated with increased risk of developing LOE, particularly when head injuries were sustained at an older age, and there was evidence for higher risk for LOE after a greater number of prior head injuries and after more severe head injuries. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that an increased risk of late-onset epilepsy is associated with head injury and that this risk increases further with multiple and more severe head injuries.

Mortality of dementia and its major subtypes in urban and rural communities of Beijing.

OBJECTIVE: To identify the mortality and epidemiological pattern of dementia and its various major subtypes among urban and rural senior residents in Beijing. METHODS: Based on Beijing's dementia prevalence survey among residents aged 55 years and above in 1997, respondents were selected by stratified multiple-stage cluster sampling and 12 urban communities and 17 rural village communities were randomly sampled then follow-up in 2001. COX regression was used to analyze relative risks controlling confounding factors on deaths of dementia cases. RESULTS: The mortality of dement patients in the 55-64 age-group was 0.82/100 person-year. The age-standardized mortality of dement cases was 0.90/100 person-year. The mortality in the 65 and above age-group was 1.44/100 person-year, and the age-standardized mortality was 1.56/100 person-year. Among AD cases, the above two mortalities were 0.35/100 and 0.42/100 person-year respectively, and among VaD cases, 0.34/100 and 0.36/100 person-year respectively. For both AD and VaD cases, their mortality increased with age. Region, gender and age were more significant to survival of AD cases. CONCLUSION: One major subtype of dementia, AD, among elderly urban and rural residents in Beijing, has a different mortality and epidemiological pattern from VaD.

Association between white matter hyperintensities, cortical volumes, and late-onset epilepsy.

OBJECTIVE: To identify the association between brain vascular changes and cortical volumes on MRI and late-onset epilepsy. METHODS: In 1993-1995, 1,920 participants (median age 62.7, 59.9% female) in the community-based Atherosclerosis Risk in Communities (ARIC) Study underwent MRI, and white matter hyperintensities were measured. In addition, in 2011-2013, 1,964 ARIC participants (median age 72.4, 61.1% female) underwent MRI, and cortical volumes and white matter hyperintensities were measured. We identified cases of late-onset epilepsy (starting at age 60 or later) from ARIC hospitalization records and Medicare claims data. Using the 1993-1995 MRI, we evaluated the association between white matter hyperintensities and subsequent epilepsy using survival analysis. We used the 2011-2013 MRI to conduct cross-sectional logistic regression to examine the association of cortical volumes and white matter hyperintensities with late-onset epilepsy. All models were adjusted for demographics, hypertension, diabetes, smoking, and APOE ε4 allele status. RESULTS: Ninety-seven ARIC participants developed epilepsy after having an MRI in 1993-1995 (incidence 3.34 per 1,000 person-years). The degree of white matter hyperintensities measured at ages 49-72 years was associated with the risk of late-onset epilepsy (hazard ratio 1.27 per age-adjusted SD, 95% confidence interval [CI] 1.06-1.54). Lower cortical volume scores were associated cross-sectionally with higher odds of late-onset epilepsy (odds ratio 1.87, 95% CI 1.16-3.02) per age-adjusted SD. CONCLUSIONS: This study demonstrates associations between earlier-life white matter hyperintensities on MRI and later-life incident epilepsy, and between cortical volumes measured later in life and late-onset epilepsy. These findings may help illuminate the causes of late-onset epilepsy.

Association of white matter microstructural integrity with cognition and dementia.

Late-life measures of white matter (WM) microstructural integrity may predict cognitive status, cognitive decline, and incident mild cognitive impairment (MCI) or dementia. We considered participants of the Atherosclerosis Risk in Communities study who underwent cognitive assessment and neuroimaging in 2011-2013 and were followed through 2016-2017 (n = 1775 for analyses of prevalent MCI and dementia, baseline cognitive performance, and longitudinal cognitive change and n = 889 for analyses of incident MCI, dementia, or death). Cross-sectionally, both overall WM fractional anisotropy and overall WM mean diffusivity were strongly associated with baseline cognitive performance and risk of prevalent MCI or dementia. Longitudinally, greater overall WM mean diffusivity was associated with accelerated cognitive decline, as well as incident MCI, incident dementia, and mortality, but WM fractional anisotropy was not robustly associated with cognitive change or incident cognitive impairment. Both cross-sectional and longitudinal associations were attenuated after additionally adjusting for likely downstream pathologic changes. Increased WM mean diffusivity may provide an early indication of dementia pathogenesis.

[123I]Ioflupane imaging in Caucasians and non-Caucasians: Are there any differences?

PURPOSE OF THE REPORT: To compare diagnostic performance of [123I]ioflupane SPECT imaging in different racial groups. In previous registration trials of [123I]ioflupane, 99% of the subjects enrolled were Caucasians. MATERIALS AND METHODS: A multicenter retrospective case-control study was conducted to evaluate whether the diagnostic performance of [123I]ioflupane SPECT imaging is different in non-Caucasians than in Caucasians matched by age, sex, and final clinical diagnosis. Subjects who had received an initial diagnosis of suspected Parkinson's disease (PD) or essential tremor (ET) and then underwent [123I]ioflupane SPECT imaging to assist with the subject's final clinical diagnosis were enrolled. Each subject's image was rated as normal or abnormal by 3 blinded expert readers. The majority interpretation was then compared with the final clinical diagnosis. Diagnostic performance of [123I]ioflupane SPECT imaging (as measured by positive percent agreement (equivalent to sensitivity), negative percent agreement (equivalent to specificity), overall percent agreement (OPA), and measures of inter-rater agreement) were compared between the Caucasian and non-Caucasian groups. RESULTS: In total, 102 non-Caucasians (58 with PD and 44 with ET as a final clinical diagnosis) and 102 Caucasians (58 with PD, 43 with ET, and 1 with "other") were included in the intent-to-diagnose (ITD) population. There was no significant difference between Caucasians and non-Caucasians in the diagnostic performance of [123I]ioflupane SPECT imaging as measured by sensitivity, specificity, OPA, and measures of inter-rater agreement. CONCLUSION: In this study, the diagnostic performance of [123I]ioflupane SPECT imaging was comparable between Caucasians and non-Caucasians.

Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results: Of the 10 420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ε4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ε4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

Diffusion tensor imaging of normal appearing white matter and its correlation with cognitive functioning in mild cognitive impairment and Alzheimer's disease.

Diffusion tensor imaging (DTI) was used to examine the microstructural integrity of normal appearing white matter (NAWM) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Significant frontal, temporal, and parietal white matter diffusion tensor changes were demonstrated in MCI and AD compared with normal controls. These changes were correlated with cognitive functioning, and are consistent with a hypothesized loss of axonal processes in affected regions.

MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson-Lewy body dementias.

OBJECTIVES: MRI assessments were correlated with serial Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC). Vascular-MCI (VMCI), Neurodegenerative MCI (NMCI) and Parkinson-Lewy body MCI (PLB-MCI) were compared during conversions to dementia. Mild cognitive impairments (MCI) are identifiable prodromes for all dementia subtypes. MRI abnormalities are characterized among MCI subjects prodromal for dementia of Alzheimer's disease (DAT), vascular dementia (VaD) and Parkinson-Lewy body dementia (PLBD). METHODS: Aging volunteers (n=166) were recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia. Cognitively normal (CN, n=52), MCIs of neurodegenerative (N-MCI, n=30), vascular (V-MCI, n=35) and Parkinson-Lewy Body (PLB-MCI, n=8) subtypes, plus converted DAT (n=19), VaD (n=17) and PLBD (n=5) were all diagnosed according to established protocol recommendations. Cerebral MRI abnormalities were likewise intercorrelated utilizing quantitative volumetric measurements. RESULTS: V-MCI and converted VaD showed extensive leukoaraiosis with more lacunar infarcts than subjects with N-MCI or PLB-MCI. N-MCI, prodromal for DAT, showed medial temporal atrophy, greater enlargement of temporal horns, and fewer vascular lesions. PLB-MCI, prodromal for PLBD, displayed third ventricular enlargement greater than N-MCI and V-MCI, with similar but less severe atrophy of medial temporal lobe than N-MCI and fewer vascular lesions than V-MCI. Cognitive Impairments due to PLB with vascular features (V-PLB-CI) showed more lacunar and microvascular lesions involving both white matter and basal ganglia with greater frontal horn enlargement. CONCLUSIONS: This study confirms different MCI subtypes prior to conversion to different dementias listed, recognizable by specific MRI abnormalities.

Impaired Cerebral Autoregulation-A Common Neurovascular Pathway in Diabetes may Play a Critical Role in Diabetes-Related Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of progressive degenerative dementia. The hallmark pathological features include beta amyloid deposition and neurofibrillary tangles. There has been a strong association of AD with Diabetes (DM) based on human studies and animal experiments. The hallmark features of AD seem to have an exaggerated presence in AD with DM, especially type 2 diabetes (T2D). In addition, insulin resistance is a common feature in both diseases and as such AD has been called type 3 diabetes. Furthermore, impairment of cerebral autoregulation has been reported in both animal and human diabetic subjects. Cerebral vascular impairment has also been implicated in the pathophysiology of AD. There is an urgent need to develop animal models of AD and DM to explore the neuropathological mechanisms of these disease and utilize such models to develop treatment strategies.

Midlife and Late-Life Vascular Risk Factors and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study.

BACKGROUND: Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity. METHODS AND RESULTS: We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity. CONCLUSIONS: Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life.

MRI abnormalities associated with mild cognitive impairments of vascular (VMCI) versus neurodegenerative (NMCI) types prodromal for vascular and Alzheimer's dementias.

BACKGROUND AND OBJECTIVES: Mild Cognitive Impairments (MCIs) are identifiable clinical entities, in neurodegenerative forms, as prodromal for Alzheimer's type (DAT) or in vascular forms, as prodromal for vascular dementia (VaD). The present longitudinal study compares and contrasts MRI abnormalities among MCI subjects as they progress to DAT versus VaD. Subjects converting to DAT and VaD confirmed ultimate diagnosis during MCI staging. In "mixed cases" the predominant MRI pathology was judged the primary cause. SUBJECTS AND METHODS: Subjects (n = 153) were selected from elderly outpatient volunteers who have been enrolled for 25 years in planned longitudinal studies of aging, stroke and dementia. Cognitively normal (CN, n = 52), MCI of neurodegenerative (N-MCI, n = 30) and vascular (V-MCI), n = 35) subtypes, plus converted DAT (n = 19) and VaD (n = 17) were diagnosed according to established protocols. Combined Mini-Mental-Cognitive Capacity Screening Examinations (CMC) screened, identified and confirmed MCIs or dementias. Cerebral MRI abnormalities were analyzed utilizing volumetric measurements and visual rating scales. RESULTS: Compared with persistently cognitively normal subjects, MCI subjects and converted dementias were significantly older without significant gender differences, but cognitively impaired subjects were older than the CN group since age is a risk factor for cognitive decline. Histories of hypertension, heart disease, diabetes mellitus, TIAs and strokes were more frequent among subjects with VMCI and VaD, confirming that all vascular risk factors contribute to vascular cognitive decline, but since vascular risk factors were treated, not all progressed to VAD. Family history of neurodegenerative disease, particularly DAT, were more prevalent among NMCI and converted DAT subjects. VMCI showed more extensive leucoaraiosis and lacunar infarcts than subjects with NMCI. NMCI, prodromal for dementia of Alzheimer's type (DAT), showed more medial temporal lobe atrophy with enlarged temporal horns, and fewer vascular lesions.

Progression of mild cognitive impairment to Alzheimer's or vascular dementia versus normative aging among elderly Chinese.

To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimer's type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed to determine prevalence and incidence of dementia and its major subtypes in Beijing, China were re-examined after an interval of approximately 3 years, repeating the same investigation protocol as at baseline. MCI subjects meeting criteria for dementia and the two major subtypes, DAT and VaD were identified at follow-up evaluation. Annual conversion rates for combined dementias and for major subtypes of DAT and VaD, from MCI, were compared with conversion rates among CN subjects. Relative risks for conversion from MCI to major subtypes of dementia were also compared with CN subjects by Cox regression models. 175 MCI and 400 CN subjects were identified at baseline. Among 121 MCI subjects available at follow-up, 51 were diagnosed with dementia (29 with DAT, 18 with VaD and 4 with other dementias), compared with 14(10 DAT, 3 VaD and 1 other type dementia) diagnosed as dementia among 281 CN subjects available at follow-up. Annual conversion rates calculated from MCI to all dementias, compared with conversion rates from CNs, were 14.1% versus 1.6%. Specifically for DAT, annual conversion rates were 8.0% versus 1.1% and for VaD were 5.0% versus 0.3%. Relative risks for developing all dementias, DAT and VaD among MCI subjects were 9, 6 and 5 times greater than among CN subjects. Conversion rates among MCI subjects to dementia, and major subtypes, for elderly Chinese residents of Beijing were comparable with results reported among similar studies worldwide. Risks of developing dementia, and major subtypes, among MCI subjects in Beijing were significantly higher than among normal subjects. Identification of MCI among elderly populations provides the possibilities for dementia prevention and treatment within prodromal stages.

MRI identifies MCI subtypes: vascular versus neurodegenerative.

As life expectancy increases worldwide, pandemics of cognitive impairment and dementia are emerging as major public health problems. Mild cognitive impairment (MCI), prodromal for dementia, is a descriptive term used for those clinical states showing early and subtle cognitive decline among the elderly, preceding the dementias. Psychometric screening combining Mini-Mental Status (MMSE) and Cognitive Capacity Screening (CCSE) Examinations, when combined now called CMC with C standing for Combined, M for MMSE, and C for CCSE, confirms diagnosis of MCI. Individuals identified with MCI are at increased risk for dementia of Alzheimer's type (DAT), vascular dementia (VAD) and other rare neurodegenerative dementias, including Lewy body dementia (LBD), fronto-temporal dementia (FTD) and Parkinson's disease dementia (PDD). Depending on different clinical compositions of cohorts studied, and MCI criteria used, between 19% and 50% of MCI progress to dementia within 3-5 years, two thirds to Alzheimer's (DAT) and one third to vascular types (VAD) in the United States. Not all Parkinsonians become demented, but PDD develops in 20-30%, however, PDD subjects were excluded from the present study, as were LBD and FTD. The incidence of MCI in those over age 70, with confirmed cognitive declines when tested 2 years later, is around 23%, but some spontaneously improve.