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J Neurol Neurosurg Psychiatry

. 2017 Jan;88(1):7-11. doi: 10.1136/jnnp-2016-313271. Epub 2016 Jun 3.

Cerebral microbleeds and neuropsychiatric symptoms in an elderly Asian cohort

Xin Xu 1 2, Qun Lin Chan 1 2, Saima Hilal 1 2, Win King Goh 1 2, Mohammad Kamran Ikram 3, Tien Yin Wong 4 5, Ching-Yu Cheng 5, Christopher Li-Hsian Chen 1 2, Narayanaswamy Venketasubramanian 2 6

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• PMID: 27261503

•  DOI: 10.1136/jnnp-2016-313271

Abstract

Objectives: Neuropsychiatric symptoms (NPS) are commonly found in patients with cerebral small vessel disease such as white matter hyperintensities and lacunar infarcts. However, the association between cerebral microbleeds (CMBs) and NPS has not been examined. Hence the present study sought to investigate the relation between CMBs and NPS in an elderly population.

Methods: This is a cross-sectional study of elderly Asians living in the community, who were assessed on a comprehensive neuropsychological battery and underwent clinical examinations as well as brain MRI scans. The 12-item neuropsychiatric inventory (NPI) was administered to a reliable informant. Total scores for individual symptoms and for NPI global performance were calculated and compared across three groups: no CMB, presence of 1 CMB and presence of multiple CMBs, controlling for demographics, vascular risk factors and other MRI markers.

Results: A total of 802 participants were included in the analysis. Participants with multiple CMBs had higher NPI total score compared to those with no CMB (1.06 vs 2.66, p=0.03). On individual symptom scores, higher score on depression (0.16 vs 0.53, p=0.02) and disinhibition (0.01 vs 0.14, p=0.04) was found in those elderly with multiple CMBs, independent of demographic and vascular risk factors, history of stroke, and other small vessel and large vessel disease markers.

Conclusions: The presence of multiple CMBs is associated with high global neuropsychiatric disorder burden, in particular symptoms of depression and disinhibition. Future studies are recommended to investigate the importance of CMBs in the pathogenesis and longitudinal progression of neuropsychiatric disorders in the general elderly population.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

• Cited by 15 articles

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2

J Alzheimers Dis

. 2020;73(3):1053-1062. doi: 10.3233/JAD-190999.

Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects

Cheuk Ni Kan 1 2, Bibek Gyanwali 1 2, Saima Hilal 1 2 3 4, Kok Pin Ng 5, Narayanaswamy Venketasubramanian 6, Christopher Li-Hsian Chen 1 2, Xin Xu 2 7

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• PMID: 31884482

•  DOI: 10.3233/JAD-190999

Abstract

Background: Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited.

Objective: This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort.

Methods: 170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Neuropsychiatric Inventory (NPI) was used to measure NPS. Generalized estimating equations modelling evaluated the relationship between NPI change and SVD progression. Logistic regression evaluated the risk of incident cognitive decline with both SVD and NPS. All models were adjusted for demographics, baseline cerebrovascular diease, and medial temporal lobe atrophy.

Results: Higher NPI scores were associated with higher SVD burden at baseline. Subjects with WMH progression had greater increase in total NPI (β[SE] = 0.46[0.19], p = 0.016), driven by hyperactivity subsyndrome (β[SE] = 0.88[0.34], p = 0.007). Subjects with incident CMBs had greater increase in psychosis subsyndrome (β[SE] = 0.89[0.30], p < 0.001). Subjects with progressions in both SVD and NPS were more likely to develop cognitive decline over 2 years (OR[95% CI] = 4.17[1.06-16.40], p < 0.05).

Conclusion: Our findings support worsening of NPS as a clinical indicator of SVD progression and are associated with cognitive decline over 2 years. Early detection of NPS and targeted interventions on SVD burden may improve NPS outcomes.

Keywords: Cerebral small vessel disease; Neuropsychiatric Inventory; cognitive impairment; dementia; lacune; microbleeds; neurobehavioral symptoms; white matter hyperintensities.

• Cited by 5 articles

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3

Front Psychiatry

. 2021 Aug 3:12:688685. doi: 10.3389/fpsyt.2021.688685. eCollection 2021.

Diagnosis and Assessment of Apathy in Elderly Chinese Patients With Cerebral Small Vessel Disease

Hóngyi Zhào 1 2, Yu Liu 3, Zhenxi Xia 1, Hongyang Xie 1, Yonghua Huang 1

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• PMID: 34413797

•  PMCID: PMC8368720

•  DOI: 10.3389/fpsyt.2021.688685

Abstract

Objective: The study aimed to estimate the frequency of apathy in Chinese patients with cerebral small vessel disease (CSVD) and investigate the relationship between apathy and neuroimaging markers of CSVD. Methods: A total of 150 CSVD aged patients were recruited for a cross-sectional observational study. Following the new revised version of diagnostic criteria for apathy (DCA), each patient was evaluated successively by the neuropsychiatric inventory (NPI-apathy), geriatric depression scale (GDS), and caregiver burden scale (CBS). The MRI presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces were rated independently. Furthermore, presence of all these MRI markers were summed in a score of 0-4 representing all CSVD features combined. Results: According to the DCA, we found that the frequency of apathy in Chinese Alzheimer's disease patients reached 37.33%, with lack of and diminished goal-directed activities in the dimension of behavior/cognition. We did not find a close relationship between apathy and depression. Caregiver burden was positively correlated with apathy severity. Apathy, but not depression, was positively associated with total CSVD burden, rather than a separate MRI marker of CSVD. Conclusion: As a key component of neuropsychiatric symptoms, apathy was common in Chinese elderly with CSVD, more attention should be paid to apathy in clinical practice of CSVD.

Keywords: aging; apathy; cerebral small vessel disease; depression; neuropsychiatric disorder.

Copyright © 2021 Zhào, Liu, Xia, Xie and Huang.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

• Cited by 2 articles

• 35 references

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4

Stroke

. 2024 Jul;55(7):1869-1876. doi: 10.1161/STROKEAHA.123.045344. Epub 2024 May 31.

Prestroke Cognitive Impairment: Frequency and Association With Premorbid Neuropsychiatric, Functional, and Neuroimaging Features

Francesco Mele 1, Ilaria Cova 1, Alessia Nicotra 1, Giorgia Maestri 1, Emilia Salvadori 2, Valentina Cucumo 1, Federico Masserini 2, Martina Martelli 2, Simone Pomati 1, Pierluigi Bertora 2, Leonardo Pantoni 1 2

Affiliations Expand

• PMID: 38818731

•  PMCID: PMC11198949

•  DOI: 10.1161/STROKEAHA.123.045344

Abstract

Background: Some patients with stroke have prestroke cognitive impairment (pre-SCI), but its etiology is not clear. The aim of this cross-sectional study was to assess the frequency of pre-SCI and its association with premorbid neuropsychiatric, functional, and neuroimaging features.

Methods: Patients hospitalized in stroke unit with an informant who could complete IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) were included. Pre-SCI was diagnosed if the IQCODE score was >3.3. Prestroke assessment also included NPI-Q (Neuropsychiatric Inventory Questionnaire), the basic Activities of Daily Living and Instrumental Activities of Daily Living scales, and the Clinical Dementia Rating scale. A multivariate logistic regression model was used to evaluate the association of pre-SCI with age, sex, education, arterial hypertension, atrial fibrillation, white matter lesions, cerebral microbleeds, and pathological medial temporal lobe atrophy.

Results: IQCODE was available in 474 of 520 patients (91.2%; 45% women; mean age 75.5±13.3 years). Pre-SCI had a prevalence of 32.5% and was associated with prestroke NPI-Q (pre-SCI absent versus present, 1.7±2.3 versus 5.5±4.9; P<0.001), Activities of Daily Living scale (0.3±0.8 versus 1.8±1.9; P<0.001), Instrumental Activities of Daily Living scale (0.6±1.3 versus 3.8±4.0; P<0.001), and Clinical Dementia Rating scale score (0.7±1.7 versus 7.2±6.2; P<0.001). In the 271 patients with a magnetic resonance imaging available, the multivariate logistic regression showed that age (odds ratio [OR], 1.05 [95% CI, 1.62-9.73]), white matter lesions (OR, 1.26 [95% CI, 1.003-1.58]), and a pathological medial temporal lobe atrophy score (OR, 3.97 [95% CI, 1.62-9.73]) were independently associated with pre-SCI. In the 218 patients with ischemic stroke, white matter lesions (OR, 1.34 [95% CI, 1.04-1.72]) and medial temporal lobe atrophy (OR, 3.56 [95% CI, 1.38-9.19]), but not age, were associated with pre-SCI.

Conclusions: One-third of patients admitted to a stroke unit have pre-SCI that is associated with preexisting neuropsychiatric symptoms and functional performance. White matter lesions and medial temporal lobe atrophy are associated with pre-SCI, suggesting that both small vessel disease and neurodegeneration might be involved in its etiology.

Keywords: cognitive dysfunction; ischemic stroke; neuroimaging; prevalence; white matter.

Conflict of interest statement

Disclosures A. Nicotra and G. Maestri have been partially supported by a liberal donation from PIAM Pharmaceutics Italy to the Department of Biomedical and Clinical Sciences, Neuroscience Research Center, University of Milan. The other authors report no conflicts.

• 29 references

• 1 figure

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5

Int J Stroke

. 2022 Feb;17(2):218-225. doi: 10.1177/17474930211006294. Epub 2021 Apr 7.

Long-term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore

Xin Xu 1 2, Cheuk Ni Kan 2, Christopher Li-Hsian Chen 2 3, Saima Hilal 2 4

Affiliations Expand

• PMID: 33724091

•  DOI: 10.1177/17474930211006294

Abstract

Background: Cortical cerebral microinfarcts are a small vessel disease biomarker underlying cognitive impairment and dementia. However, it is unknown whether cortical cerebral microinfarcts are associated with neuropsychiatric disturbances, and whether its effects are independent of conventional small vessel disease markers.

Aims: We investigated the associations of cortical cerebral microinfarcts burden with incidence and progression of neuropsychiatric subsyndromes in a memory clinic cohort of elderly in Singapore.

Methods: In this prospective cohort, 496 subjects underwent detailed neuropsychological and clinical assessments, 3T brain MRI, and Neuropsychiatric Inventory assessment at baseline and two years later. Cortical cerebral microinfarcts and other small vessel disease markers, including white matter hyperintensities, lacunes, and microbleeds, were graded according to established criteria. Neuropsychiatric symptoms (NPS) were clustered into subsyndromes of hyperactivity, psychosis, affective, and apathy following prior findings. Functional decline was determined using the clinical dementia rating (CDR) scale.

Results: The presence of multiple cortical cerebral microinfarcts (≥2) was associated with higher total NPS scores (β = 4.19, 95% CI = 2.81-5.58, p < 0.001), particularly hyperactivity (β = 2.01, 95% CI = 1.30-2.71, p < 0.01) and apathy (β = 1.42, 95% CI = 0.65-2.18, p < 0.01) at baseline. Between baseline and year-2, multiple cortical cerebral microinfarcts were associated with accelerated progression in total NPS scores (β = 0.29, 95% CI = 0.06-0.53, p = 0.015), driven by hyperactivity (β = 0.45, 95% CI = 0.17-0.72, p < 0.01). Subjects with multiple cortical cerebral microinfarcts also had a faster functional decline, as measured with the CDR-sum-of-boxes scores, when accompanied with progression (β = 0.31, 95% CI = 0.11-0.51, p < 0.01) or hyperactivity in total NPS (β = 0.34, 95% CI = 0.13-0.56, p < 0.01).

Conclusion: Cortical cerebral microinfarcts are associated with incidence and progression of geriatric neurobehavioral disturbances, independent of conventional small vessel disease markers. The impact of incident cortical cerebral microinfarcts on neurocognitive and neuropsychiatric trajectories warrants further investigations.

Keywords: Cortical microinfarcts; cerebrovascular disease; dementia; neuroimaging; neuropsychiatric symptoms.

• Cited by 2 articles

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6

Stroke

. 2016 Dec;47(12):3041-3044. doi: 10.1161/STROKEAHA.116.014418. Epub 2016 Nov 10.

Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy

Sanneke van Rooden 1, Anna M van Opstal 1, Gerda Labadie 1, Gisela M Terwindt 1, Marieke J H Wermer 1, Andrew G Webb 1, Huub A M Middelkoop 1, Steven M Greenberg 1, Jeroen van der Grond 2, Mark A van Buchem 1

Affiliations Expand

• PMID: 27834748

•  PMCID: PMC5127744

•  DOI: 10.1161/STROKEAHA.116.014418

Abstract

Background and purpose: Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary cerebral hemorrhage with amyloidosis-Dutch type.

Methods: Twenty-seven DNA-proven Dutch-type mutation carriers (15 symptomatic and 12 presymptomatic) (mean age of 45.9 years) and 33 controls (mean age of 45.6 years) were included. 7T and 3T MRI was performed, cerebral amyloid angiopathy and small-vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand and on the other, mutation status, adjusted for age, sex, and education.

Results: In symptomatic patients, all established cerebral amyloid angiopathy MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities, and dilated perivascular spaces in centrum semiovale) were increased compared with controls (P<0.05). In presymptomatic subjects, the prevalence of microinfarcts and median volume of white matter hyperintensities were increased in comparison to controls (P<0.05). Symptomatic patients performed worse on all cognitive domains, whereas presymptomatic subjects did not show differences in comparison with controls (P<0.05).

Conclusions: White matter hyperintensities and microinfarcts are more prevalent among presymptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages.

Keywords: cerebral amyloid angiopathy; cognition; hemorrhage; magnetic resonance imaging; siderosis.

© 2016 American Heart Association, Inc.

• Cited by 21 articles

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