Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias

Yarchoan, Mark; Xie, Sharon X.; Kling, Mitchel A.; Toledo, Jon B.; Wolk, David A.; Lee, Edward B.; Deerlin, Vivianna M. Van; Lee, Virginia M.‐Y.; Trojanowski, John Q.; Arnold, Steven E.

doi:10.1093/brain/aws271

Cited by 226 publications

(176 citation statements)

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“…Therefore, individuals with heavy cerebrovascular pathology are not enrolled in ADNI and vascular pathology is underrepresented, although it is a common finding in patients with dementia. 37,38 An unexpected finding was that the percentage of participants with SMC did not vary between the different SCI and the CN groups, although it was 10% higher in the executive SCI group. Larger samples might be needed to assess whether individuals with SMC are at higher risk of having SCI.…”

mentioning

confidence: 94%

Memory, executive, and multidomain subtle cognitive impairment

Toledo¹,

Bjerke

Chen³

et al. 2015

Neurology

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Objective: We studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group. Methods:We studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants.Results: Using a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively. Conclusions:Our results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) patternbased analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment. Neurology ® 2015;85:144-153 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; aHV 5 adjusted hippocampal volume; CN 5 cognitively normal; FDG 5 fluorodeoxyglucose; HC 5 healthy control; MCI 5 mild cognitive impairment; MRI-SPARE-AD 5 MRI Spatial Pattern of Abnormalities for Recognition of Early Alzheimer Disease; PET-HCI 5 PET hypometabolic convergence index; p-tau181 5 tau phosphorylated at threonine 181; ROI 5 region of interest; SCI 5 subtle cognitive impairment; SCINIB 5 subtle cognitive impairment with normal neuronal injury biomarkers; SMC 5 subjective memory complaints; SNAP 5 suspected nonamyloid pathology; t-tau 5 total tau; WMI 5 white matter hyperintensity.The development of different neuropsychological batteries and biomarkers and their use in different cohorts have led to the study of earlier stages of dementia. Therefore, mild cognitive impairment (MCI) was defined as a stage that may precede Alzheimer disease (AD) or other dementias. MCI is characterized by moderate cognitive impairment without impairment of daily living activities, 1 that can be further categorized based on the cognitive profile into amnestic and nonamnestic MCI subtypes. Biomarkers correlate with neuropathologic hallmarks of AD 2-4 and a model of biomark...

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mentioning

confidence: 94%

Memory, executive, and multidomain subtle cognitive impairment

Toledo¹,

Bjerke

Chen³

et al. 2015

Neurology

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“…Association between HTN and AD may be additive or synergistic, producing a more severe cognitive degradation [9]. Necroptic studies of patients with AD showed more atherosclerotic lesions in cerebral vessels associated with more amyloid plaques and neurofibrillary tangles [19,20]. Brain of hypertensive patients has increased amyloid plaques and neurofibrillary tangles [21].…”

Section: Ad and Htnmentioning

confidence: 99%

Cardiovascular Alterations in Patients with Dementia

2017

JCCR

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Submit Manuscript | http://medcraveonline.com one of the most susceptible being the brain [1]. Hypertension is a major risk factor for vascular cognitive impairment (VCI) and for Alzheimer disease (AD), the most frequent causes of dementia in the elderly [3]. Continuous elevation in blood pressure has progressive effects on the structure and function of cerebral arteries determining adaptive changes like remodeling, aiming to decrease the mechanical stress on the arterial wall [4]. Remodeling could be hypertrophic or eutrophic and reduces the vesselsˈ lumen increasing the vascular resistance and represents a potential risk factor for cardiovascular and cerebrovascular disease [5].Old hypertension also induces an increase in the stiffness of large arteries which is a good predictor of cognitive decline and stroke and is associated with silent brain lesions [3,6]. HTN is a major risk factor for atherosclerosis. Increase in BP increases the odds of complex aortic atherosclerosis, predictive of ischemic strokes [7]. Atherosclerotic lesions are localised at the site of turbulence of the flow like the carotid bifurcation and the vertebrobasilar system and less frequently in intracranial arteries. Stroke can be produced by releasing fragments from atherosclerotic plaques (artery-to-artery embolism) or by rupture and hemorrhage with acute cerebrovascular occlusions.HTN also provokes small vessel disease (SVD) in which the most frequent pathological substrate is arteriolosclerosis [8], affecting the deep hemispheric white matter and basal ganglia. One of the pathological features of arteriosclerosis is lipohyalinosis [8] and in advanced lesions rupture of the vessel with microscopic or macroscopic hemorrhages disposed typically in basal ganglia or thalamus. Capillary rarefaction induces lesions in the periventricular white matter. Brain alterations underlying VCIVCI includes a spectrum of cognitive alterations due to cerebrovascular factors, ranging from mild to full blown vascular dementia impairing the daily lifeˈs activities [3]. A major cause of cognitive impairment is stroke. Having a stroke doubles the risk of dementia (poststroke dementia) [3]. The risk of VCI is incresed in patients with no history of stroke but with brain infarcts (silent infarcts) at imagistic investigations. Strategic-infarct dementia is produced by a single stroke affecting a region important for cognition like the frontal lobe or the thalamus [3]. Multi-infarct dementia can also results from multiple strokes destroying large amounts of brain tissue [3]. SVD is a major cause of VCI, being responsible for up to 45 % of dementia cases [3]. Neuropathological alterations caused by cerebral SVD linked with VCILacunar infarcts: Are rounded, < 20 mm diameter lesions, founded more frequently in the basal ganglia, associated with SVD and a strong predictor of VCI [11]. They are caused by acute occlusion of small perforating cerebral arteries or embolism from upstream vessels [12]. Recent studies show the possibility that blood-brain barrier (BBB) alte...

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“…В ряде исследований показана связь между альцгеймеровскими изменениями и атеро-склерозом крупных экстра-и интракраниальных артерий [17][18][19], но не патологией мелких сосудов [20][21][22]. Тем не менее проспективно было показа-но, что прирост количества амилоидных бляшек связан с уменьшением эластичности сосудистой стенки и ареактивностью сосудов [23].…”

Section: β-амилоид и сосудистые факторы рискаunclassified

Twenty-five years of the amyloid hypothesis of alzheimer disease: advances, failures and new perspectives

Левин¹,

Васенина²

2016

Z. nevrol. psikhiatr. im. S.S. Korsakova

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115 лет назад -25 ноября 1901 г. -51-летняя женщина А. Дитер была доставлена во Франкфурт-скую муниципальную лечебницу «для лунатиков и эпилептиков», где обратила на себя внимание 37-летнего психиатра А. Альцгеймера (1864-1915) необычными для ее возраста быстро нарастающими нарушениями памяти, речи, параноидными рас-стройствами. 110 лет назад -в 1906 г. Альцгеймер на заседании общества психиатров юго-запада Гер-мании в Тюбенгене представил сообщение о клини-ческих проявлениях и патоморфологических наход-ках, выявленных у умершей к тому времени паци-ентки. При аутопсии с помощью разработанной не-давно методики импрегнации серебром А. Альцгей-doi: 10.17116/jnevro2016116623-9 25 лет амилоидной гипотезе происхождения болезни Альцгеймера: достижения, неудачи и новые перспективы О.С. ЛЕВин*, Е.Е. ВаСЕнина ГБОУ ДПО «Российская медицинская академия последипломного образования», Москва, Россия амилоидная гипотеза развития болезни альцгеймера (Ба) продолжает доминировать, однако за свою 25-летнюю историю концепция значительно изменилась. Оказалось, что накопление β-амилоида связано не только с повышением его продукции (как казалось после открытия генетических механизмов части семейных случаев Ба), но и с нарушением его клиренса из ткани головного мозга, который осуществляется при помощи микроциркуляторной системы. При этом наиболее патогенную роль в веществе мозга играют не сами сенильные бляшки, описанные а. альцгеймером почти 110 лет назад и состоящие из нерастворимых конъюгатов, а растворимые олигомеры β-амилоида. Связь сосудистого и дегенеративного процессов при Ба подтверждают единство факторов риска, а также клинические, нейровизуализацион-ные, патоморфологические и экспериментальные данные. Одним из звеньев, связующих дегенеративный и сосудистый процессы при Ба, служит инсулинорезистентность. исходя из современного состояния амилоидной гипотезы обсуждаются вопросы новых мультимодальных стратегий терапии Ба. Ключевые слова: β-амилоид, болезнь Альцгеймера, артериосклероз, инсулинорезистентность, мультимодальная терапия. Twenty-five years of the amyloid hypothesis of Alzheimer's disease: advances, failures and new perspectivesO.S. Levin, e.e. vaSenina Russian Medical academy of Postgraduate education, Moscow, Russia amyloid hypothesis of alzheimer's disease (aD) has been long the primary one. During the 25-year history the concept has been dramatically changed. accumulation of β-amyloid is associated not only with the disruption of its synthesis (as it seemed after the discovery of genetic mechanisms of some familial cases of aD) but rather with the disruption of its clearance and elimination from the brain tissue via the microcirculatory system. it has been recognized that soluble oligomers of β-amyloid, but not senile plaques that consisted of insoluble conjugates described by a. alzheimer 100 years ago, play a key pathogenic role in the brain. interrelation of vascular and degenerative processes is confirmed by common risk factors, clinical, neuroimaging, pathomorphological and experimental data. insulin-resis...

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Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias

Cited by 226 publications

References 48 publications

Memory, executive, and multidomain subtle cognitive impairment

Memory, executive, and multidomain subtle cognitive impairment

Cardiovascular Alterations in Patients with Dementia

Twenty-five years of the amyloid hypothesis of alzheimer disease: advances, failures and new perspectives

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