Erratum to: Implication of Small Vessel Disease MRI Markers in Alzheimer’s Disease and Lewy Body Disease

Background: Small vessel disease (SVD) magnetic resonance imaging (MRI) markers including deep and periventricular white matter hyperintensities (PWMH), lacunes, and microbleeds are frequently observed in Alzheimer’s disease (AD) and Lewy body disease (LBD), but their implication has not been clearly elucidated. Objective: To investigate the implication of SVD MRI markers in cognitively impaired patients with AD and/or LBD. Methods: We consecutively recruited 57 patients with pure AD-related cognitive impairment (ADCI), 49 with pure LBD-related cognitive impairment (LBCI), 45 with mixed ADCI/LBCI, and 34 controls. All participants underwent neuropsychological tests, brain MRI, and amyloid positron emission tomography. SVD MRI markers including the severity of deep and PWMH and the number of lacunes and microbleeds were visually rated. The relationships among vascular risk factors, SVD MRI markers, ADCI, LBCI, and cognitive scores were investigated after controlling for appropriate covariates. Results: LBCI was associated with more severe PWMH, which was conversely associated with an increased risk of LBCI independently of vascular risk factors and ADCI. PWMH was associated with attention and visuospatial dysfunction independently of vascular risk factors, ADCI, and LBCI. Both ADCI and LBCI were associated with more lobar microbleeds, but not with deep microbleeds. Conclusion: Our findings suggest that PWMH could reflect degenerative process related with LBD, and both AD and LBD independently increase lobar microbleeds.

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Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

Journal of the International Neuropsychological Society ◽

10.1017/s1355617709990816 ◽

2009 ◽

Vol 15 (6) ◽

pp. 898-905 ◽

Cited By ~ 25

Author(s):

AIHONG ZHOU ◽

JIANPING JIA

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Domains ◽

Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

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Small Vessel Disease, but Neither Amyloid Load nor Metabolic Deficit, Is Dependent on Age at Onset in Alzheimer’s Disease

Biological Psychiatry ◽

10.1016/j.biopsych.2014.01.019 ◽

2015 ◽

Vol 77 (8) ◽

pp. 704-710 ◽

Cited By ~ 9

Author(s):

Marion Ortner ◽

Alexander Kurz ◽

Panagiotis Alexopoulos ◽

Florian Auer ◽

Janine Diehl-Schmid ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Small Vessel Disease ◽

Age At Onset ◽

Small Vessel ◽

Vessel Disease ◽

Amyloid Load

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Neuropsychological differentiation of small vessel disease, Alzheimer's disease and mixed dementia

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(02)00254-x ◽

2002 ◽

Vol 203-204 ◽

pp. 17-22 ◽

Cited By ~ 24

Author(s):

Klaus Schmidtke ◽

Michael Hüll

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Small Vessel Disease ◽

Small Vessel ◽

Mixed Dementia ◽

Vessel Disease

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Staging: Relevance for Trial Design in Vascular Burden of the Brain

International Psychogeriatrics ◽

10.1017/s1041610203009256 ◽

2003 ◽

Vol 15 (S1) ◽

pp. 231-239 ◽

Cited By ~ 1

Author(s):

Barry Reisberg ◽

Steven H. Ferris ◽

Thet Oo ◽

Emile Franssen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Small Vessel Disease ◽

Small Vessel ◽

Clinical Staging ◽

Progressive Dementia ◽

Vessel Disease ◽

Vascular Burden ◽

The Brain ◽

Clinical Continuum

Cerebrovascular small vessel disease is now believed to be the major source of vascular burden of the brain. Cerebrovascular small vessel disease and Alzheimer's disease appear to represent pathophysiologic and clinical continua, rather than dichotomous entities. It appears that common etiopathologic mechanisms underlie the clinical presentation of both of these conditions. Therefore, the staging procedures that have been developed for the clinical continuum of age-associated memory impairment, mild cognitive impairment, and the progressive dementia of Alzheimer's disease appear to be applicable for the same continua in cerebrovascular small vessel disease. Although temporal and prognostic aspects have been studied for the Alzheimer's-related portions of this clinical staging continuum, they remain to be elucidated for cerebrovascular small vessel disease.

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Ventricular expansion, white matter hyperintensities, and global cognition in Alzheimer’s disease and normal aging

10.1101/2020.11.30.20240879 ◽

2020 ◽

Author(s):

Sabrina Adamo ◽

Joel Ramirez ◽

Melissa F. Holmes ◽

Fuqiang Gao ◽

Ljubica Zotovic ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Normal Aging ◽

Small Vessel ◽

Cognitive Test ◽

Vessel Disease ◽

Link Type

ABSTRACTBackgroundThe progression of Alzheimer’s Disease (AD) may be tracked by measuring the growth of the ventricular cerebrospinal fluid (vCSF) over time. AD is commonly comorbid with markers of cerebral small vessel disease (SVD), viewed on MRI as white matter hyperintensities (WMH). Larger WMH volumes are correlated with poorer cognitive test scores. Additionally, periventricular WMHs have a proposed relationship to the vCSF.PurposeThis study will examine ventricular expansion and its associations between periventricular/deep WMH and cognition in AD and normal aging.MethodsBaseline and 1-year follow-up data were collected from AD (n=117) and cognitively normal control (NCs; n=49) participants taking part in the Sunnybrook Dementia Study. MRI (1.5T) and scores from both the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS) were assessed at each time point. Volumetric data was generated using a semi-automated pipeline and each individual’s vCSF and WMHs were transformed to an intermediate space to determine volumetric growth. Regressions were used to determine relationships between vCSF growth measures, SVD burden, and cognition, accounting for demographics and individual interscan intervals.ResultsThe AD group displayed 14.6% annual ventricular growth as opposed to NC who had only 11.8% annual growth. AD showed significant growth in vCSF (p < 0.001), a trend toward greater pWMH growth (p = 0.06) and no difference in dWMH growth volumes compared to NC. vCSF growth was positively associated with pWMH (β = 0.32, p < 0.001) but not dWMH growth in AD while in NC it was associated with both pWMH (β = 0.48, p < 0.001) and dWMH growth (β = 0.35, p = 0.02). In AD, vCSF growth was associated with the both the MMSE (β = -0.30, p < 0.001) and the DRS (β = -0.31, p < 0.001) in separate models.ConclusionsThe findings from this study suggest that in just under 1.5 years, the significantly rapid ventricular expansion observed in AD may be closely related to periventricular small vessel disease. As vCSF growth rates are an important biomarker of AD neurodegeneration that corresponds with cognitive decline, future research should further explore atrophy associated with periventricular vasculopathy.Trial RegistrationClinicalTrials.gov, NCT01800214. Registered on 27 February 2013.

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Frontal white matter lesions in Alzheimer’s disease are associated with both small vessel disease and AD-associated cortical pathology

Acta Neuropathologica ◽

10.1007/s00401-021-02376-2 ◽

2021 ◽

Author(s):

Kirsty E. McAleese ◽

Mohi Miah ◽

Sophie Graham ◽

Georgina M. Hadfield ◽

Lauren Walker ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Regional Differences ◽

Small Vessel Disease ◽

White Matter Lesions ◽

Small Vessel ◽

Published Data ◽

Axonal Loss ◽

Vessel Disease

AbstractCerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer’s disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aβ burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.

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