The contribution of cerebral vascular neuropathology to mild stage of Alzheimer’s dementia using the NACC database

2021 ◽  
Vol 18 ◽  
Author(s):  
Yue Liu ◽  
Daniel Chan ◽  
John D Crawford ◽  
Perminder S Sachdev ◽  
Nady Braidy
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
White Matter ◽  
Late Life ◽  
Alzheimer’S Dementia ◽  
Significant Relation ◽  
Alzheimer's Dementia ◽  
Vessel Disease ◽  
Global Cognition ◽  
Cerebral Vascular

Background: The interaction between cerebral vessel disease (CVD) pathology and Alzheimer’s disease (AD) pathology in the development of dementia is controversial. We examined the association of cerebral vascular neuropathology and cerebrovascular risk factors with the mild stage of Alzheimer's dementia and cognitive function. Methods: This cross-sectional study included men and women aged 60 years or over who had yearly clinical assessments and had agreed to brain autopsy at the time of death, and who contributed to data stored at the National Alzheimer's Coordinating Center (NACC) in the USA. Cognitively normal and impaired subjects with presumptive aetiology of AD, including mild cognitive impairment (ADMCI) and dementia (Alzheimer’s dementia), and with complete neuropathological data, were included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Systematic neuropathological assessments documenting the severity of cerebral vascular pathology were included. Logistic and linear regression analyses corrected for age at death, sex and Lewy body pathology were used to examine associations of vessel disease with the severity of Alzheimer's disease dementia, and cognitive function, respectively. Results: No significant relationship was observed between late-life risk factors and Alzheimer’s dementia. The severity of arteriosclerosis and presence of global infarcts/lacunes were related to mild Alzheimer’s dementia (B=0.423, p<0.001;B=0.366, p=0.026), and the effects were significant after adjusting for neuritic plaques and neurofibrillary tangles (B=0.385, p<0.001;B=0.63, p=0.001). When vascular brain injuries were subdivided into old and acute/subacute types, we found that old microinfarcts and old microbleeds were associated with mild Alzheimer’s dementia (B=0.754, p=0.007; B=2.331, p=0.032). The old microinfarcts remained significantly associated with mild Alzheimer’s dementia after correcting AD pathologies (B=1.31, p<0.001). In addition, the number of microinfarcts in the cerebral cortex had a significant relation with mild Alzheimer’s dementia, whether or not the data were corrected for AD pathologies (B=0.616, p=0.016; B=0.884, p=0.005). Atherosclerosis, arteriosclerosis and white matter rarefaction were found to be significantly associated with faster progression of Alzheimer’s dementia (B=0.068, p=0.001; B=0.046, p=0.016, B=0.081, p=0.037), but white matter rarefaction no longer had a significant effect after adjusting for AD pathologies. We also found that the severity of atherosclerosis was related to impairment in processing speed (β=-0.112, p=0.006) and executive function (β=-0.092, p=0.023). Arteriosclerosis was significantly associated with language (β=-0.103, p=0.011) and global cognition (β=-0.098, p=0.016) deficits. Conclusion: Our study found the significant relation of global, old, acute/subacute and regional cerebral vascular pathologies, but not white matter rarefaction, to the onset and severity of Alzheimer’s dementia. We also showed that late-life risk factors were found to have no relation with Alzheimer’s dementia, and the increased risk of dementia with APOE ε4 is not mediated by CVD. The best interpretation of these findings is that CVD has an additive effect with AD pathologies in the development and progression of what is clinically diagnosed as Alzheimer’s dementia, and it is very likely that CVD and AD are to a major degree independent pathologies.

scholarly journals The association of Lewy bodies with limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes and their role in cognition and Alzheimer’s dementia in older persons

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sonal Agrawal ◽  
Lei Yu ◽  
Sukriti Nag ◽  
Konstantinos Arfanakis ◽  
Lisa L. Barnes ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Older Persons ◽  
Lewy Bodies ◽  
Alzheimer’S Dementia ◽  
Community Dwelling ◽  
Alzheimer's Dementia ◽  
Cognitive Domains ◽  
Age Related ◽  
Global Cognition

AbstractLewy bodies (LBs) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are common in older persons and associated with cognitive impairment. However, little is known about the relationship between LBs and LATE-NC and their combined roles in cognitive impairment and Alzheimer’s dementia in community-dwelling participants. The study included 1670 community-based participants (mean age-at-death, 89.5 years (SD = 6.65); 69% females) who underwent annual assessments of cognition to create summary measures of global cognition and cognitive domains and evaluation for Alzheimer’s dementia. Systematic neuropathologic evaluations were performed to assess LBs, LATE-NC, and Alzheimer’s disease (AD) pathology. We excluded cases with pathologically confirmed frontotemporal lobar degeneration in this study. Logistic and linear regression analyses were used, adjusted for demographics and AD pathology. LBs were present in 428 (25.6%) decedents (29 nigra-predominant, 165 limbic-type, and 234 neocortical-type) while 865 (51.7%) decedents exhibited LATE-NC (307 stage 1, 167 stage 2, and 391 stage 3). LBs combined with LATE-NC were common (15% of all participants) and in those with Alzheimer’s dementia (25%). Neocortical-type, but not nigral-predominant or limbic-type LBs increased the odds of stage 2/3 LATE-NC (odds ratio = 1.70; 95% confidence interval = 1.26–2.30). The association between neocortical-type LBs and stage 2/3 LATE-NC was stronger in those under 90 years of age and in women. In analyses of cognition and Alzheimer’s dementia, LATE-NC and neocortical-type LBs, separately, were related to lower global cognition, five specific cognitive domains, and an increased odds of Alzheimer’s dementia, above and beyond the AD pathology. Limbic-type LBs were related to lower global cognition, and the domains of episodic, working, and semantic memory, and increased odds of Alzheimer’s dementia. Furthermore, there was no interaction between limbic/neocortical-type LBs and LATE-NC on cognitive function, cognitive domains, or Alzheimer’s dementia. These findings suggest that neocortical-type LBs are associated with LATE-NC, specifically in the younger old and in women. Limbic/neocortical-type LBs and LATE-NC have separate and additive effects on cognitive function and odds of Alzheimer’s dementia.

scholarly journals Vascular risk factors and incident late-life depression in a Korean population

2006 ◽  
Vol 189 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Jae-Min Kim ◽  
Robert Stewart ◽  
Sung-Wan Kim ◽  
Su-Jin Yang ◽  
Il-Seon Shin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Density Lipoprotein ◽  
Late Life ◽  
Diagnostic Interview ◽  
Affective States ◽  
Late Life Depression ◽  
Lower Baseline ◽  
Vascular Status

BackgroundCausal relationships between vascular factors and late-life depression are controversial.AimsTo investigate prospective associations between risk factors for vascular disease and incidence of late-life depression.MethodOf 661 community participants aged 65 years or over, without depression at baseline, 521 (79%) were re-evaluated 2 years later. At baseline and follow-up, a diagnostic interview for depression was carried out and information on vascular status, disability and cognitive function was gathered.ResultsPre-existing heart disease, incident stroke and lower baseline high-density lipoprotein cholesterol level were significantly associated with incidence of late-life depression, independently of disability and cognitive function.ConclusionsThese results provide some support for a vascular aetiology of late-life depression. However, important risk factors for cerebrovascular disease such as hypertension and diabetes were not implicated, and the associations with lipid levels might still be explained by affective states earlier in life.

scholarly journals Vascular lesions and functional limitations among older adults: does depression make a difference?

2014 ◽  
Vol 26 (9) ◽  
pp. 1501-1509 ◽  
Author(s):  
Celia F. Hybels ◽  
Carl F. Pieper ◽  
Lawrence R. Landerman ◽  
Martha E. Payne ◽  
David C. Steffens
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
White Matter ◽  
Functional Impairment ◽  
Functional Limitations ◽  
Late Life ◽  
Cognitive Status ◽  
Cerebral White Matter ◽  
Late Life Depression ◽  
Increased Risk

ABSTRACTBackground:The association between disability and depression is complex, with disability well established as a correlate and consequence of late life depression. Studies in community samples report that greater volumes of cerebral white matter hyperintensities (WMHs) seen on brain imaging are linked with functional impairment. These vascular changes are also associated with late life depression, but it is not known if depression is a modifier in the relationship between cerebrovascular changes and functional impairment.Methods:The study sample was 237 older adults diagnosed with major depression and 140 never depressed comparison adults, with both groups assessed at study enrollment. The dependent variable was the number of limitations in basic activities of daily living (ADL), instrumental ADLs, and mobility tasks. The independent variable was the total volume of cerebral white matter lesions or hyperintensities assessed though magnetic resonance imaging.Results:In analyses controlling for age, sex, race, high blood pressure, and cognitive status, a greater volume of WMH was positively associated with the total number of functional limitations as well as the number of mobility limitations among those older adults with late life depression but not among those never depressed, suggesting the association between WMH volume and functional status differs in the presence of late life depression.Conclusions:These findings suggest older patients with both depression and vascular risk factors may be at an increased risk for functional decline, and may benefit from management of both cerebrovascular risk factors and depression.

scholarly journals Vascular disease/risk and late-life depression in a Korean community population

2004 ◽  
Vol 185 (2) ◽  
pp. 102-107 ◽  
Author(s):  
Jae-Min Kim ◽  
Robert Stewart ◽  
Il-Seon Shin ◽  
Jin-Sang Yoon
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Vascular Disease ◽  
Disease Risk ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Late Life ◽  
Late Life Depression ◽  
Previous Stroke ◽  
Community Population

BackgroundAssociations between vascular risk factors and late-life depression are controversial.AimsTo investigate the association between measures of vascular disease/ risk and depression and confounding and effect modification by APOE genotype and cognitive function.MethodIn a Korean community population aged 65+ (n=732), diagnosis of depression (Geriatric Mental State Schedule) and information on vascular status, disability, APOE genotype and cognitive function were obtained.ResultsPrevious stroke and lower high-density lipoprotein cholesterol level (but neither hypertension nor diabetes) were significantly associated with depression (independently of disability and cognitive function). These associations were stronger in participants with borderline cognitive impairment, although not to a significant extent.ConclusionsExcept for previous stroke and an atherogenic lipid profile, associations between depression and other common risk factors for cerebrovascular disease were not evident.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis

Stroke ◽  
2021 ◽  
Author(s):  
Jessica W. Lo ◽  
John D. Crawford ◽  
David W. Desmond ◽  
Hee-Joon Bae ◽  
Jae-Sung Lim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Older Age ◽  
Individual Participant Data ◽  
Individual Participant ◽  
Global Cognition

Background and Purpose: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. Methods: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. Results: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033]; P <0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=−0.078 SD/year [95% CI, −0.11 to −0.045]; P <0.001 for global cognition in a subgroup analysis). Conclusions: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

scholarly journals CNS small vessel disease

Neurology ◽  
2019 ◽  
Vol 92 (24) ◽  
pp. 1146-1156 ◽  
Author(s):  
Rocco J. Cannistraro ◽  
Mohammed Badi ◽  
Benjamin H. Eidelman ◽  
Dennis W. Dickson ◽  
Erik H. Middlebrooks ◽  
...  
Keyword(s):  
Risk Factors ◽  
White Matter ◽  
Small Vessel Disease ◽  
Blood Oxygenation ◽  
Small Vessel ◽  
Imaging Biomarkers ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Advanced Imaging ◽  
Vessel Disease

CNS small vessel disease (CSVD) causes 25% of strokes and contributes to 45% of dementia cases. Prevalence increases with age, affecting about 5% of people aged 50 years to almost 100% of people older than 90 years. Known causes and risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. CSVD can be asymptomatic; however, depending on location, lesions can cause mild cognitive dysfunction, dementia, mood disorders, motor and gait dysfunction, and urinary incontinence. CSVD is diagnosed on the basis of brain imaging biomarkers, including recent small subcortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Advanced imaging modalities can detect signs of disease even earlier than current standard imaging techniques. Diffusion tensor imaging can identify altered white matter connectivity, and blood oxygenation level-dependent imaging can identify decreased vascular reactivity. Pathogenesis is thought to begin with an etiologically specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit. Uncertainties regarding pathogenesis have delayed development of effective treatment. The most widely accepted approach to treatment is to intensively control well-established vascular risk factors, of which hypertension is the most important. With better understanding of pathogenesis, specific therapies may emerge. Early identification of pathologic characteristics with advanced imaging provides an opportunity to forestall progression before emergence of symptoms.

scholarly journals White Matter and Neuroprotection in Alzheimer’s Dementia

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 503 ◽  
Author(s):  
Luca Lorenzini ◽  
Mercedes Fernandez ◽  
Vito Antonio Baldassarro ◽  
Andrea Bighinati ◽  
Alessandro Giuliani ◽  
...  
Keyword(s):  
White Matter ◽  
Alzheimer’S Dementia ◽  
Oligodendrocyte Precursor Cells ◽  
Resonance Imaging ◽  
Alzheimer's Dementia ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Main Component ◽  
Preclinical And Clinical Studies

Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in Alzheimer’s dementia (AD) and other neurodegenerative diseases, alterations which are early, extended, and regionally selective. Given that the white matter turnover is considerable in the adulthood, and that myelin repair is currently recognized as being the only true reparative capability of the mature CNS, oligodendrocyte precursor cells (OPCs), the cells that differentiate in oligodendrocyte, responsible for myelin formation and repair, are regarded as a potential target for neuroprotection. In this review, several aspects of the OPC biology are reviewed. The histology and functional role of OPCs in the neurovascular-neuroglial unit as described in preclinical and clinical studies on AD is discussed, such as the OPC vulnerability to hypoxia-ischemia, neuroinflammation, and amyloid deposition. Finally, the position of OPCs in drug discovery strategies for dementia is discussed.

scholarly journals An Atypical Cutaneous Reaction to Rivastigmine Transdermal Patch

2011 ◽  
Vol 2011 ◽  
pp. 1-2 ◽  
Author(s):  
T. Grieco ◽  
M. Rossi ◽  
V. Faina ◽  
I. De Marco ◽  
P. Pigatto ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Side Effects ◽  
Cholinesterase Inhibitor ◽  
Alzheimer’S Dementia ◽  
Cutaneous Reaction ◽  
Transdermal Patch ◽  
Alzheimer's Dementia ◽  
Rivastigmine Patch ◽  
Cutaneous Side Effects

Rivastigmine is a cholinesterase inhibitor which improves cognitive function and is currently being used in patients with mild to moderate Parkinson's and Alzheimer's dementia. This drug can be given orally or topically, as transdermal patch. The latter form is currently used for most excellent compliance and few side effects. The most common cutaneous side effects are irritative dermatitis. We report the second case of active sensitization by the rivastigmine-patch in a patient suffering from Alzheimer's dementia.

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