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The Utility of the National Alzheimer's Coordinating Center's Database for the Rapid Assessment of Evolving Neuropathologic Conditions.

ABSTRACT: The field of dementia research is rapidly evolving, especially with regards to our understanding of the diversity of neuropathologic changes that underlie cognitive decline. Definitions and criteria for known conditions are being periodically revised and refined, and new findings are being made about neuropathologic features associated with dementia status. The database maintained by the National Alzheimer's Coordinating Center (NACC) offer researchers a robust, rapid, and statistically well-powered method to evaluate the implications of newly identified neuropathologic conditions with regards to comorbidities, demographic associations, cognitive status, neuropsychologic tests, radiographic findings, and genetics. NACC data derive from dozens of excellent US Alzheimer disease research centers, which collectively follow thousands of research volunteers longitudinally. Many of the research participants are autopsied using state-of-the-art methods. In this article, we describe the NACC database and give examples of its use in evaluating recently revised neuropathologic diagnoses, including primary age-related tauopathy (PART), limbic predominant age-related TDP-43 encephalopathy (LATE), and the preclinical stage of Alzheimer disease neuropathologic change, based on the National Institute on Aging-Alzheimer's Association consensus guidelines. The dementia research community is encouraged to make use of this readily available database as new neuropathologic changes are recognized and defined in this rapidly evolving field.

SUBMITTER: Mock C

PROVIDER: S-EPMC7242145 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Diabetes is a risk factor for the development of cognitive impairment and possibly for accelerated progression to Alzheimer disease (AD) and other dementias, though the trajectory of cognitive decline in general and in specfic cognitive domains by diabetes is unclear. METHODS:Using the National Alzheimer's Coordinating Center's Uniform Data Det (NACC-UDS) to identify cohorts of elders with normal cognition (N = 7,663) and mild cognitive impairment (MCI, N = 4,114), we compared overall cognitive composite and domain specific sub-scores and their progression over time between diabetic and non-diabetic subjects. RESULTS:Diabetes was more common among those with MCI (14.7%) than among subjects who were cognitively normal (11.7%). In subjects who were cognitively normal, baseline cognitive composite scores, attention, and executive function sub-scores were lower in diabetics than non-diabetics (by 0.098, 0.066, and 0.015 points, respectively). Over time, cognitive composite score showed subtle worsening in non-diabetics (0.025 points every 6 months), with an additional worsening of 0.01 points every 6 months in diabetics compared to non-diabetics. In the MCI groups, baseline cognitive composite as well as attention and executive domain sub-scores were lower in diabetics than non-diabetics (by 0.078, 0.092, and 0.032 points, respectively). Over time, cognitive composite (by 0.103 points every 6 months) and all domain specific sub-scores showed subtle worsening in non-diabetics, but diabetics had significantly slower worsening than non-diabetics on both cognitive composite (by 0.028 points) and domain specific sub-scores. DISCUSSION:Among elders, diabetes may be associated with lower cognitive performance, primarily in non-memory domains. However it is not associated with continued worsening, suggesting a static deficit with minimal memory involvement. This data suggest that diabetes may contribute more to a vascular profile of cognitive impairment than a profile more typical of AD.

Project description:BackgroundNeuropsychiatric symptoms (NPSs) are common in Alzheimer's disease (AD). NPSs contribute to patients' distress, caregiver burden, and institutionalization. White matter hyperintensities (WMHs) appear on magnetic resonance imaging, usually indicative of cerebrovascular disease. WMHs have been associated with certain NPSs. We aimed to assess the relationship between WMH and NPS severity in mild cognitive impairment (MCI) due to AD (MCI-AD) and in AD and to assess the ability of WMHs to predict NPS progression. Data were obtained from the National Alzheimer's Coordinating Center.MethodsA total of 252 participants (114 with MCI-AD and 138 with AD) were used in this study. Baseline WMHs were quantified using an automated segmentation technique. NPSs were measured using the Neuropsychiatric Inventory. Mixed-effect models and correlations were used to determine the relationship between WMHs and NPSs.ResultsLongitudinal mixed-effect models revealed a significant relationship between increase in Neuropsychiatric Inventory total scores and baseline WMHs (p = .014). There was a significant relationship between baseline WMHs and an increase in delusions (p = .023), hallucinations (p = .040), agitation (p = .093), depression (p = .017), and irritability (p = .002). Correlation plot analysis showed that baseline whole-brain WMHs predicted change in future Neuropsychiatric Inventory total scores (r = .169, p = .008) and predicted change in future agitation severity scores (r = .165, p = .009). WMHs in the temporal lobes (r = .169, p = .008) and frontal lobes (r = .153, p = .016) contributed most to this change.ConclusionsDepression, irritability, and agitation are common NPSs and very distressful to patients and caregivers. Our findings of increased NPS severity over time in MCI-AD and AD with increased WMHs have important implications for treatment, arguing for aggressive treatment of vascular risk factors in patients with MCI-AD or AD.

Project description:Cerebrovascular disease and vascular risk factors are associated with Alzheimer's disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer's Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer's disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, ?-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 'unremarkable brain' cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that ?-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer's disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer's disease and patients with ?-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer's disease than in other neurodegenerative disorders, especially in younger subjects, and lowers the threshold for dementia due to Alzheimer's disease and ?-synucleinopathies, which suggests that these disorders should be targeted by treatments for cerebrovascular disease.

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The Utility of the National Alzheimer's Coordinating Center's Database for the Rapid Assessment of Evolving Neuropathologic Conditions.

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