Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease

Ikeda, Masaki; Kodaira, Sayaka; Kasahara, Hiroo; Takai, Eriko; Nagashima, Kazuaki; Fujita, Yukio; Makioka, Kouki; Hirayanagi, Kimitoshi; Furuta, Natsumi; Furuta, Masaya; Sanada, Etsuko; Kobayashi, Akito; Harigaya, Yasuo; Nagamine, Shun; Hattori, Noriaki; Tashiro, Yuichi; Kishi, Kazuhiro; Shimada, Hironori; Sakai, Takayuki; Tanaka, Hisashi; Sakai, Yusuke; Yamazaki, Tsuneo; Tanaka, Yukiko; Aihara, Yasuo; Amari, Masakuni; Yamaguchi, Hideyo; Okamoto, Koichi; Takatama, Masamitsu; Higuchi, Tetsuya; Tsushima, Yoshito; Ikeda, Yoshio

doi:10.3389/fneur.2021.543866

Cited by 8 publications

(10 citation statements)

References 57 publications

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“…In a recent study with MCI patients, the prevalence of CMBs was 45% and reached 67% in subjects with an amnesic profile [ 11 ]. In patients with other types of dementia, such as primary progressive aphasia, a prevalence of 28% was observed and reached 50% in cases of logopenic aphasia [ 3 , 27 ] or between 16.9 and 45.2% in Lewy body dementia [ 26 , 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinical impact of microbleeds in patients with Alzheimer’s disease

et al. 2022

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Introduction Cerebral microbleeds (CMBs) are more frequent in patients with Alzheimer’s disease (AD) than in the general population. However, their clinical significance remains poorly understood. We carried out a multimodal approach to evaluate the impact of CMBs at a clinical, neuropsychological, and survival level, as well as on core AD biomarkers in the cerebrospinal fluid (CSF) in AD patients. Methods We prospectively recruited 98 patients with mild-moderate AD. At baseline, they underwent brain MRI, and AD CSF biomarkers and APOE genotypes were analysed. An extensive neuropsychological battery was performed at baseline and after 1 year of follow-up. We analysed the stroke incidence and mortality with survival analyses. Results Forty-eight (48.5%) patients had at least one CMBs. Eight (8.2%) patients had strictly nonlobar CMBs, 39 (40.2%) had any lobar CMB locations. The incidence of stroke was higher in AD patients with lobar CMBs than in those without CMBs (p < 0.05). Mortality did not differ among groups (p > 0.05). At the cognitive level, CMBs patients deteriorated more rapidly at 12 months according to MMSE scores, with no differences observed at 24 months. We did not observe differences in the other tests, except for an increase in caregiver burden in the CMBs group. The presence of cerebral amyloidosis and APOE ε4 were associated with a greater presence of CMBs. Conclusion CMBs are associated with an increased risk of ischemic stroke in AD patients without differences in mortality. Patients with CMBs did not seem to have different consequences associated with cognitive decline except for an increase in caregiver overload.

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Section: Discussionmentioning

confidence: 99%

“…Cerebral microbleeds (CMBs) are lesions appearing as hyposignals on susceptibility weighted imaging (SWI) magnetic resonance sequences that reflect leakage of blood products and haemosiderin deposits from cerebral vessels damaged by Aβ deposition [ 3 ]. They may be related to hypertension or cerebral amyloid angiopathy (CAA).…”

Section: Introductionmentioning

confidence: 99%

Clinical impact of microbleeds in patients with Alzheimer’s disease

et al. 2022

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“…Keeping the above limitations in mind, biomarkers are not useful only in research, but also in clinical practice, showing both added and prognostic value [78,79]. They are not only able to confirm the presence of AD in typical cases, but they are able to identify AD in cases with atypical presentations such as primary progressive aphasia, corticobasal syndrome and posterior cortical atrophy [34,35,80,81]. Correct recognition of Alzheimer's disease (not just amyloid pathology) helps to avoid administration of aducanumab (or any other anti-amyloid antibody) in non-AD patients, and makes possible the use of such disease-modifying treatments in clinically atypical AD patients.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

Paraskevas

Kapaki

2021

Brain Sciences

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Correct in vivo diagnosis of Alzheimer’s disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer’s pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations.

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“…Lobar cerebral microbleeds (CMB) in lvPPA affected temporal, frontal and parietal lobes with left side predominance, while CMB volume decreased in the left temporal area. Aberrant brain perfusion in lvPPA may be derived from brain atrophy and may involve aberrant microcirculation caused by lobar CMBs and cerebrovascular injuries (Ikeda et al 2021). However, individual PPA cases with ADNC exist where distribution of plaques and NFTs do not account for this specific phenotype (Gefen et al 2012).…”

Section: Pathobiology Of Other Ad Variantsmentioning

confidence: 99%

Recent update on the heterogeneity of the Alzheimer’s disease spectrum

Jellinger¹

2021

J Neural Transm

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Alzheimer's disease (AD), the most common form of dementia worldwide, is a mixed proteinopathy (β-amyloid, tau and other proteins). Classically defined as a clinicopathological entity, AD is a heterogeneous, multifactorial disorder with various pathobiological subtypes showing different forms of cognitive presentation, currently referred to as the Alzheimer spectrum or continuum. Its morphological hallmarks are extracellular β-amyloid (amyloid plaques) and intraneuronal tau aggregates forming neurofibrillary tangles and neurites, vascular amyloid deposits (cerebral amyloid angiopathy), synapse and neuronal loss as well as neuroinflammation and reactive astrogliosis, leading to cerebral atrophy and progressive mental/cognitive impairment (dementia). In addition to "classical" AD, several subtypes with characteristic regional patterns of tau pathology have been segregated that are characterized by distinct clinical features, differences in age, sex distribution, disease duration, cognitive status, APOE genotype, and biomarker levels. In addition to four major subtypes based on the distribution of tau pathology and brain atrophy (typical, limbic predominant, hippocampal sparing, and minimal atrophy), several other clinical variants (non-amnestic, corticobasal, behavioral/dysexecutive, posterior cortical variants, etc.) have been identified. These heterogeneous AD variants are characterized by different patterns of key neuronal network destructions, in particular the default-mode network that is responsible for cognitive decline. Other frequent age-related co-pathologies, e.g., cerebrovascular lesions, Lewy and TDP-43 pathologies, hippocampal sclerosis, or argyrophilic grain disease, essentially influence the clinical picture and course of AD, and can challenge our understanding of this disorder including the threshold and causal relevance of each individual pathology. Unravelling the clinico-morphological heterogeneity among the AD spectrum entities is important for better elucidation of the pathogenic mechanisms affecting the aging brain that may enable a broader diagnostic coverage of AD as a basis for implementing precision medicine approaches and for developing preventive and ultimately disease-modifying therapies for this devastating disorder.

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Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease

Cited by 8 publications

References 57 publications

Clinical impact of microbleeds in patients with Alzheimer’s disease

Clinical impact of microbleeds in patients with Alzheimer’s disease

Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

Recent update on the heterogeneity of the Alzheimer’s disease spectrum

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