Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study

BACKGROUND: Both types of cerebral white matter hyperintensities, periventricular (PVL) and deep white matter lesions (DWML) have been previously associated with the development of depression in older subjects. However, it remains controversial as to whether PVL, DWML, or both are most strongly associated with depression and this was the aim of the current study. METHODS: In a pan-European multicentre study of 626 older subjects, we examined the relationship between PVL and DWML, depressive symptoms (GDS quintile), cognitive status (MMSE), hypertension and history of stroke. RESULTS: In univariate analysis we found that depressive symptoms as assessed by GDS were associated with both types of white matter lesions (Spearman rho = 0.12 p = 0.002 for DWML and rho = 0.09 p = 0.01 for PVL). Using ordinal logistic regression analysis the total DWML score (p = 0.041), rather than PVL (p = 0.9) was found to predict GDS scores. CONCLUSIONS: DWML, but not PVL, were most strongly associated with depressive symptoms in this sample. As DWML (unlike PVL) are associated with vascular ischaemic damage, our findings are consistent with the 'vascular depression' hypothesis. Longitudinal studies are needed to clarify the time course of these relationships, in particular, whether modifying DWML alters the natural history of depression.     

White matter volumes and periventricular white matter hyperintensities in aging and dementia

OBJECTIVE: To determine the relationship between MRI periventricular white matter hyperintensities, cerebral white matter volumes, neuropathologic findings, and cognitive status in aged individuals. BACKGROUND: The significance of periventricular white matter hyperintensities seen on MR images in aged individuals remains controversial. The Nun Study is a longitudinal cohort aging study in which all 678 initially enrolled participants agreed to autopsy neuropathologic examination. METHODS: We used MRI to measure white matter volumes of the cerebral hemispheres in 52 formaldehyde-fixed brains for correlation with white matter and neocortical pathology, postmortem MRI observations, and cognitive measures. RESULTS: Reduced white matter volume is associated with dementia, but periventricular white matter hyperintensities were not related to white matter volume, stroke, or dementia. CONCLUSIONS: Our results do not support the hypothesis that periventricular hyperintensities seen on MR images have deleterious consequences in these aged individuals.     

Depressive symptoms and white matter changes in patients with dementia

OBJECTIVE: The aim of the present study was to investigate if depressive symptoms in demented patients are associated with white matter changes (WMCs) in the brain. BACKGROUND: WMCs are frequently found in patients with dementia, as well as among elderly nondemented patients with depressive symptoms. However, it is less established whether or not WMCs are related to depressive symptoms in demented patients. METHODS: 67 (26 men, 41 women) patients with primary degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The patients were young-old (mean 68.1, SD 7.3). All patients underwent a standardized examination procedure and MRI of the brain. The degree of WMCs was visually rated, blindly. Depressive symptoms were rated according to the Gottfries-Br?ne-Steen scale (anxiety, fear-panic, depressed mood). RESULTS: No significant relationship was found between WMCs and depressive symptoms in the demented patients. CONCLUSION: The possible involvement of WMCs in the pathogenesis of depressive symptoms in dementia is unclear. A link between disruptions of frontal-subcortical pathways, due to WMCs, and depressive symptomatology in dementia has been hypothesised from earlier findings, which would imply common elements of pathogenesis for depressive symptomatology and cognitive impairment in dementia. However, the results of the present study do not add further support to this hypothesis.     

Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy

AimsTo investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function.Methods and proceduresDiffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test).Outcomes and resultsChildren with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups.Conclusions and implicationsPeriventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.What this paper adds

• ⿢Focal white matter alterations are observed in the corticospinal tract in UCP with unilateral white matter lesions
• ⿢Diffuse white matter alterations throughout all cerebral lobes are observed in UCP with bilateral white matter lesions
• ⿢Fractional anisotropy in the posterior thalamic radiations correlates with dominant hand function

     

Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions

BACKGROUND: Carotid sinus syndrome (CSS) is a common cause of syncope in older persons. There appears to be a high prevalence of carotid sinus hypersensitivity (CSH) in patients with dementia with Lewy bodies (DLB) but not in Alzheimer's disease. OBJECTIVE: To compare the prevalence of CSH in DLB and Alzheimer's disease, and to determine whether there is an association between CSH induced hypotension and brain white matter hyperintensities on magnetic resonance imaging (MRI). METHODS: Prevalence of CSH was compared in 38 patients with DLB (mean (SD) age, 76 (7) years), 52 with Alzheimer's disease (80 (6) years), and 31 case controls (73 (5) years) during right sided supine carotid sinus massage (CSM). CSH was defined as cardioinhibitory (CICSH; >3 s asystole) or vasodepressor (VDCSH; >30 mm Hg fall in systolic blood pressure (SBP)). T2 weighted brain MRI was done in 45 patients (23 DLB, 22 Alzheimer). Hyperintensities were rated by the Scheltens scale. RESULTS: Overall heart rate response to CSM was slower (RR interval = 3370 ms (640 to 9400)) and the proportion of patients with CICSH greater (32%) in DLB than in Alzheimer's disease (1570 (720 to 7800); 11.1%) or controls (1600 (720 to 3300); 3.2%) (p<0.01)). The strongest predictor of heart rate slowing and CSH was a diagnosis of DLB (Wald 8.0, p<0.005). The fall in SBP during carotid sinus massage was greater with DLB (40 (22) mm Hg) than with Alzheimer's disease (30 (19) mm Hg) or controls (24 (19) mm Hg) (both p<0.02). Deep white matter hyperintensities were present in 29 patients (64%). In DLB, there was a correlation between magnitude of fall in SBP during CSM and severity of deep white matter changes (R = 0.58, p = 0.005). CONCLUSIONS: Heart rate responses to CSM are prolonged in patients with DLB, causing hypotension. Deep white matter changes from microvascular disease correlated with the fall in SBP. Microvascular pathology is a key substrate of cognitive impairment and could be reversible in DLB where there are exaggerated heart rate responses to carotid sinus stimulation.     

Impact of white matter changes on activities of daily living in mild to moderate dementia

The association between white matter changes and activities of daily living (ADL) in a large, well-defined cohort of patients with mild-to-moderate dementia (either Alzheimer's disease or subcortical vascular dementia) were investigated. A total of 289 patients were divided into three groups (140 mild, 99 moderate, and 50 severe) depending on the degree of white matter changes as indicated on brain magnetic resonance image scans. Further, we analyzed the three groups' performances on basic and instrumental ADL. The degree of white matter changes was associated with greater age, hypertension, previous history of stroke, higher Hachinski Ischemic Score, worse global cognitive and functional status, and an increased impairment of basic ADL and instrumental ADL. The increased impairment with regard to the severe group's performance on both the basic and instrumental ADL remained significant after adjustment for age and hypertension. Tasks involving physical activities were most significant. This was the first study investigating the association between white matter changes and ADL in a large, well-defined dementia cohort. The present study suggests that severe white matter changes may be associated with higher impairment on both basic and instrumental ADL.     

Frontal white matter lesions and dementia in lacunar infarction

We studied the associations of mental deterioration and blood pressure with severity and location of lesions in the cerebral white matter of 35 patients (27 men and eight women) aged 52-84 (mean 70.9) years with multiple lacunar infarcts; 21 had no dementia and 14 were demented. Using magnetic resonance imaging to evaluate lesion severity, we determined that demented patients had more severe lesions than nondemented patients; this difference was especially prominent for lesions in the frontal lobe (p less than 0.001). Score on the dementia rating scale of Hasegawa et al was negatively correlated with severity of the lesions in the frontal lobe. Blood pressure was positively correlated with the severity of white matter lesions. We show that severity of lesions in the white matter, especially in the frontal lobe, is correlated with mental deterioration of patients with multiple lacunar infarcts. Because uncontrolled hypertension is related to the severity of such lesions, careful selection of antihypertensive treatment is important in preventing both the cerebral lesions and the associated mental deterioration.     

Antipsychotic drug use and associations with neuropsychiatric symptoms in persons with impaired cognition: a cross-sectional study

Background: Neuropsychiatric symptoms (NPS) in cognitive disorders impair quality of life, increase caregiver stress, and may lead to earlier institutionalization and death. The objective of this study was to investigate the use of antipsychotics among persons with cognitive impairment in home care and residential care, and its associations with NPS and personal characteristics.

Methods: Data were collected in the South Savo Hospital District area with 105 000 inhabitants, where 66 of 68 institutions providing long-term residential care and 20 of 21 municipal home care producers joined the study. Nurses recorded the current use of drugs, the activities of daily living (ADL), prevalence of diagnosed dementia, and assessed the cognitive status and the prevalence of recent NPS based on the item list of the Neuropsychiatric Inventory (NPI).

Results: The study population was 1909 persons with cognitive impairment, and 1188 of them lived in residential care. Antipsychotics were used by 563 (29.5%) persons in the whole study population. In residential care 448 (37.7%) used antipsychotics and the corresponding figure in home care was 115 (15.9%). In the multivariate analysis, the antipsychotic use was associated with living in residential care, benzodiazepine use, and with NPS symptoms agitation/aggression (OR =1.70, 95% CI =1.16–2.48), disinhibition (OR =2.33, 95% CI =1.31–4.15), hallucinations (OR =2.77, 95% CI =1.69–4.55), and delusions (OR =1.71, 95% CI =1.01–2.91).

Conclusions: Antipsychotic use was common among persons with cognitive impairment. The results suggest that antipsychotics are commonly used to treat hyperactivity and psychotic symptoms, especially in residential care.     

阿尔茨海默病患者神经精神症状与脑白质高信号的相关性分析

目的 分析阿尔茨海默病（AD）患者脑白质高信号（WMH）与神经精神症状（NPSs）的相关 性。方法 选取 2021 年 4 月至 2022 年 3 月在成都市第四人民医院记忆门诊就诊的 97 例 AD 患者为研究 对象。采用简易精神状态检查（MMSE）、日常生活活动能力量表（ADL）、神经精神科问卷（NPI）评估患者 的认知功能、日常生活活动能力和 NPSs。对患者的头部进行 3T MRI 扫描后,采用 UBO-Detctor 软件提 取患者各脑区 WMH 体积。采用偏相关分析 AD 患者各脑区 WMH 体积与 MMSE、ADL、NPI 评分的相关 性。结果 97 例 AD 患者的 MMSE 评分为 11.0（5.5,19.0）分,ADL 评分为 38.0（26.0,54.0）分,NPI 评分为 16.0（3.0,34.0）分。AD 患者的 MMSE 评分与全脑、脑室周围、左侧颞叶、右侧颞叶 WMH 体积呈负相关（r= -0.240、-0.239、-0.332、-0.208;P＜ 0.05）;ADL 评分与左侧颞叶、右侧颞叶 WMH 体积呈正相关（r=0.352、 0.257;P＜ 0.05）;NPI 评分与左侧颞叶 WMH 体积呈正相关（r=0.373,P＜ 0.05）。NPI 的 12 项症状中, AD 患者妄想与左侧枕叶 WMH 体积呈正相关（r=0.214,P＜ 0.05）;幻觉、激越 / 攻击性与左侧颞叶、顶叶 WMH 体积呈正相关（r=0.354、0.212、0.460、0.254;P＜ 0.05）;焦虑、情感高涨 / 欣快、睡眠 / 夜间行为、食 欲 / 进食障碍与左侧颞叶 WMH 体积呈正相关（r=0.222、0.422、0.295、0.222;P＜ 0.05）。结论 脑白质 的损伤程度与 AD 患者的认知功能、日常生活能力及 NPSs 存在相关性,不同脑区的白质损伤与不同的 NPSs 相关,预防脑白质的损伤或能改善 AD 患者的 NPSs。     

Cerebral white matter lesions and the risk of dementia

OBJECTIVE: To study the association between white matter lesions (WML) in specific locations and the risk of dementia. DESIGN: The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. SETTING: General population. PARTICIPANTS: We included 1077 people aged 60 to 90 years who did not have dementia at baseline. MAIN OUTCOME MEASURE: Incident dementia by Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM III-R) criteria. RESULTS: During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. CONCLUSION: White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.     

Vasoreactivity in patients with periventricular white matter lucency

OBJECTIVES: Cerebral hypoperfusion has been evidenced in patients with periventricular white matter lucency (PWML), however, our knowledge is limited regarding vasoreactivity (VR) changes in these patients. Therefore, we compared the cerebral blood flow velocity (CBFV) responses during different vasoregulatory challenges in healthy volunteers, to those in patients with PWML. MATERIAL AND METHODS: In 20 patients with PWML and in 20 healthy volunteers the VR of the middle cerebral artery (MCA) system was measured by analyzing the changes of CBFV during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler (TCD) registration the systemic blood pressure, the expiratory partial CO(2) pressure (pCO(2)) and the electroencephalograph (EEG) were monitored. RESULTS: The relative velocity change was significantly smaller in the PWML group than in the normal control group during hypercapnia (16 +/- 12% vs 32 +/- 17%; P < 0.001) and this finding was confirmed by assessment of pCO(2)-corrected velocity change (4.7 +/- 3.7 cm/s/kPa vs 18.4 +/- 6.8 cm/s/KPa; P < 0.001). Although CBFV measurements during acetazolamide test tended to support these findings, the changes of other parameters measured did not reach the level of significance. One patient showed considerable orthostatic reaction (mean arterial blood pressure decrease by 70 mmHg) but it was not associated with significant changes in CBFV. CONCLUSION: Patients with PWML showed an impaired VR in the MCA flow territory supporting the concept of the microangiopathic origin of leukoaraiotic changes.     

Cerebral white matter lesions and depressive symptoms in elderly adults

BACKGROUND: There is evidence for a vascular cause of late-life depression. Cerebral white matter lesions are thought to represent vascular abnormalities. White matter lesions have been related to affective disorders and a history of late-onset depression in psychiatric patients. Their relation with mood disturbances in the general population is not known. We investigated the relation between white matter lesions and the presence of depressive symptoms or a history of depression in a population-based study. METHODS: In a sample of 1077 nondemented elderly adults, we assessed the presence and severity of subcortical and periventricular white matter lesions using magnetic resonance imaging, presence of depressive symptoms, and history of depression. Using multiple regression analysis, we examined the relation among white matter lesions, depressive symptoms, and history of depression. RESULTS: Most of the subjects had white matter lesions. Persons with severe white matter lesions (upper quintile) were 3 to 5 times more likely to have depressive symptoms as compared with persons with only mild or no white matter lesions (lowest quintile) (periventricular odds ratio [OR] = 3.3; 95% confidence interval [CI], 1.2-9.5; subcortical OR = 5.4; 95% CI, 1.8-16.5). In addition, persons with severe subcortical but not periventricular white matter lesions were more likely to have had a history of depression with an onset after age 60 years (OR = 3.4; 95% CI, 1.1-10.7) compared with persons with only mild or no white matter lesions. CONCLUSION: The severity of subcortical white matter lesions is related to the presence of depressive symptoms and to a history of late-onset depression.     

Outcome of neuropsychiatric symptoms and daily functioning of patients with dementia treated on an acute psychogeriatric ward

Abstract

Background: Dementia is associated with progressive deterioration in multiple cognitive domains, functional impairment and neuropsychiatric symptoms (NPS).

Aims: The aim of this study was to explore the factors associated with the outcome of NPS and daily functioning in patients with dementia during acute psychogeriatric hospitalization.

Materials and method: The data (n?=?175) were collected between 2009 and 2013 in naturalistic settings on one acute psychogeriatric ward at one university hospital in Finland. Behavioural symptoms were assessed using the Neuropsychiatric Inventory (NPI) and activities of daily living using the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL).

Results: During the hospital stay (45 days ±30.4) NPI total score decreased from 33.9 to 18.2 (p?<?.001). Daily functioning score decreased from 31.7 to 20.9 (p?<?.001). The number of patients taking antipsychotics (96–130, p?=?.004) and anxiolytics (54–102, p?<?.001) increased from admission to discharge. Overall mean dosage (mg/day) of antipsychotics (from 40.2 to 72.0 in chlorpromazine equivalents, p?<?.00) and anxiolytics (from 3.43 to 7.47 in diazepam equivalents, p?<?.001) also increased. Higher antipsychotic dosage at discharge was a significant predictor for large NPI score change (p?=?.002) indicating better symptom reduction. Neither higher antipsychotic dosage or anxiolytic dosage at discharge were significant predictors for ADL score change.

Conclusions: Neuropsychiatric symptoms improved while deterioration was found in daily functioning from admission to discharge. Higher antipsychotic dosage at discharge was a predictor for larger NPI score change indicating better symptom reduction. Preventing threatening ADL decline during hospital stay is especially important.     

Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects

The aim was to identify potentially treatable riskfactors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living inthe community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physicaland neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma aminoacid measurements. Brain MRI infarcts, deep white matter lesions(DWMLs), and periventricular hyperintensities were found in 26%, 43%,and 29% of the 178 participants, respectively. Subjects with DWMLswere significantly older and had a higher frequency of hypertension,higher systolic blood pressure, and more brain infarcts, but lowerplasma concentrations of tryptophan. In the multivariate model, greaterage and lower plasma tryptophan concentrations were independentlyassociated with DWMLs. Tryptophan concentrations were inversely relatedto DWML grading, whereas hypertension and brain infarction were morecommon in subjects with higher extents of DWMLs. The present studysuggests that greater age and lower plasma tryptophanconcentrations were important in producingDWMLs in elderly subjects.

     

Small deep white matter lesions are associated with right-to-left shunts in migraineurs

The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 ± 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) ≥11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56–6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.     

血管性痴呆患者神经精神症状的临床分析

目的 了解血管性痴呆患者的神经精神症状特点.方法 采用神经精神科问卷、简易智能状态检查量表和Hachinski缺血评分量表,分别评价血管性痴呆、脑卒中后非痴呆、阿尔茨海默病和正常老年人群的神经精神症状.结果 与正常对照组比较,血管性痴呆组患者在妄想、幻觉、激越、抑郁和(或)心境恶劣、情感淡漠、易激惹和(或)不稳定、迷乱的动作行为等调查内容和神经精神科问卷总评分,差异有统计学意义(P＜0.05或P＜0.01);阿尔茨海默病组伴妄想者多于血管性痴呆组,组间差异有统计学意义(P＜0.01).血管性痴呆不同严重程度组之间比较,幻觉、焦虑、情感淡漠、易激惹和(或)不稳定、迷乱的动作行为等调查项目达到统计学意义(P＜0.05或P＜0.01),且随病情的逐渐加重而症状更为明显.结论 血管性痴呆和阿尔茨海默病患者存在多种相似的神经精神症状,中至重度血管性痴呆患者表现为以情绪和情感障碍为主的神经精神症状.     

Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions

Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 ± 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 ± 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.