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Anna Poggesi,
Alida Gouw,
Wiesje van der Flier, Giovanni Pracucci,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
José M Ferro,
Michael Hennerici,
Peter Langhorne,
John T O'Brien,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Philip Scheltens,
Domenico Inzitari,
Leonardo Pantoni
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ABSTRACT: Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 ± 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.
Journal of Neurology 11/2012; · 3.47 Impact Factor
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Michael J Firbank,
Andrew Teodorczuk,
Wiesje M van der Flier,
Alida A Gouw,
Anders Wallin,
Timo Erkinjuntti,
Domenico Inzitari,
Lars-Olof Wahlund,
Leonardo Pantoni,
Anna Poggesi, Giovanni Pracucci,
Peter Langhorne,
John T O'Brien
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ABSTRACT: Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.
To investigate the relationship between baseline and incident depression and progression of white matter changes.
In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale.
Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline.
Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.
The British journal of psychiatry: the journal of mental science 05/2012; 201:40-5. · 6.62 Impact Factor
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Domenico Inzitari, Giovanni Pracucci,
Anna Poggesi,
Giovanna Carlucci,
Frederik Barkhof,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
José M Ferro,
Michael Hennerici,
Peter Langhorne,
John O'Brien,
Philip Scheltens,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Leonardo Pantoni
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ABSTRACT: To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes.
Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints.
11 European centres.
639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy.
Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score >/=2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke.
Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect.
The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.
BMJ (Clinical research ed.). 02/2009; 339:b2477.
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Anna Poggesi, Giovanni Pracucci,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
Ana Verdelho,
Michael Hennerici,
Peter Langhorne,
John O'Brien,
Philip Scheltens,
Marieke C Visser,
Milita Crisby,
Gunhild Waldemar,
Anders Wallin,
Domenico Inzitari,
Leonardo Pantoni
[show abstract]
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ABSTRACT: To investigate, in a cohort of nondisabled elderly people, the association between urinary complaints and severity of age-related white matter changes (ARWMC).
Cross-sectional data analysis from a longitudinal multinational study.
The Leukoaraiosis And DISability Study, assessing ARWMC as an independent predictor of the transition from functional autonomy to disability in elderly subjects.
Six hundred thirty-nine subjects (288 men, 351 women, mean age 74.1+/-5.0) with magnetic resonance imaging (MRI)-detected ARWMC of different severity.
ARWMC severity was graded on MRI as mild, moderate, and severe (Fazekas scale). MRI assessment also included ARWMC volumetric analysis and the count of infarcts. Urinary complaints (nocturia, urinary frequency, urgency, incontinence) were recorded based on subjects' answers to four questions.
In comparing the three ARWMC severity groups, there was a significant difference only in prevalence of urgency, with 16% of subjects in the mild severity group, 17% in the moderate severity group, and 25% in the severe group (P=.03). Adjusting for age, sex, lacunar and nonlacunar infarcts, diabetes mellitus, and use of diuretics, severe ARWMC retained an independent effect in the association with urinary urgency (odds ratio=1.74, 95% confidence interval=1.04-2.90, severe vs mild group). Subjects with urinary urgency also had higher ARWMC volumes (25.2, vs 20.4 mm(3) in those without urinary urgency; P<.001). Urgency was confirmed to be associated with the severe degree of ARWMC, irrespective of complaints of memory, gait disturbances, or history of depression.
In a cohort of nondisabled elderly people, severe ARWMC were associated with urinary urgency, independent of other potential confounders and vascular lesions of the brain.
Journal of the American Geriatrics Society 08/2008; 56(9):1638-43. · 3.74 Impact Factor
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Domenico Inzitari,
Michela Simoni, Giovanni Pracucci,
Anna Poggesi,
Anna Maria Basile,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
José M Ferro,
Michael Hennerici,
Peter Langhorne,
John O'Brien,
Frederik Barkhof,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Leonardo Pantoni
[show abstract]
[hide abstract]
ABSTRACT: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population.
We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline.
The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline.
Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.
Archives of Internal Medicine 02/2007; 167(1):81-8. · 11.46 Impact Factor
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Leonardo Pantoni,
Anna Poggesi,
Anna Maria Basile, Giovanni Pracucci,
Frederik Barkhof,
Hugues Chabriat,
Timo Erkinjuntti,
José M Ferro,
Michael Hennerici,
John O'Brien,
Reinhold Schmidt,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Domenico Inzitari
[show abstract]
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ABSTRACT: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients.
Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study.
The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people.
Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified.
Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning.
At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score.
Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.
Journal of the American Geriatrics Society 07/2006; 54(7):1095-101. · 3.74 Impact Factor
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Antonio Di Carlo,
Maria Lamassa,
Marzia Baldereschi, Giovanni Pracucci,
Domenico Consoli,
Charles D A Wolfe,
Maurice Giroud,
Anthony Rudd,
Ilse Burger,
Augusto Ghetti,
Domenico Inzitari
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ABSTRACT: Information on determinants and prognosis of ischemic stroke subtypes is scarce. We aimed at evaluating risk factors, pathogenesis, treatment and outcome of different ischemic stroke subtypes.
In a European Concerted Action involving seven countries, ischemic stroke subtypes defined according to the Oxfordshire Community Stroke Project (OCSP) were evaluated for demographics, baseline risk factors, resource use, 3-month survival, disability (Barthel Index) and handicap (Rankin Scale).
During the 12-month study period, cerebral infarction was diagnosed in 2740 patients with first-in-a-lifetime stroke (mean age 70.5+/-12.4 years, 53.4% males). OCSP classification was achieved in 2472 (90.2%). Of these, 26.7% were total anterior circulation infarctions (TACI), 29.9% partial anterior circulation infarctions (PACI), 16.7% posterior circulation infarctions (POCI) and 26.7% lacunar infarctions (LACI). In multivariate analysis, atrial fibrillation was predictive of TACI (odds ratio [OR], 1.61; 95% CI, 1.28-2.03), hypertension (OR, 1.38; 95% CI, 1.16-1.65) and myocardial infarction (OR, 1.42; 95% CI, 1.08-1.86) predictive of PACI, hypertension (OR, 1.25; 95% CI, 1.04-1.50) predictive of LACI. A negative association was observed between TACI and hypertension (OR, 0.51; 95% CI, 0.42-0.61). Discharge home was 50% less probable in TACI and PACI than in LACI patients. As compared to LACI, TACI significantly increased the risk of 3-month death (OR, 5.73; 95% CI, 3.91-8.41), disability (OR, 3.27; 95% CI, 2.30-4.66) and handicap (OR, 2.71; 95% CI, 1.91-3.85).
Ischemic stroke subtypes have different risk factors profile, with consequences on pathogenesis and prognosis. Information on determinants of the clinical syndromes may impact on prevention and acute-phase interventions.
Journal of the Neurological Sciences 06/2006; 244(1-2):143-50. · 2.35 Impact Factor
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Anna Maria Basile,
Leonardo Pantoni, Giovanni Pracucci,
Kjell Asplund,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
José M Ferro,
Michael Hennerici,
John O'Brien,
Philip Scheltens,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Domenico Inzitari
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ABSTRACT: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard.
The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years.
Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade.
The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
Cerebrovascular Diseases 02/2006; 21(5-6):315-22. · 2.72 Impact Factor
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Marco Inzitari,
Antonio Carlo,
Marzia Baldereschi, Giovanni Pracucci,
Stefania Maggi,
Carlo Gandolfo,
Salvatore Bonaiuto,
Gino Farchi,
Emanuele Scafato,
Pierugo Carbonin,
Domenico Inzitari
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ABSTRACT: To examine risk and predictors of motor-performance (MP) decline targeting subjects performing normally at an initial observation.
Cohort study.
A subsample of the Italian Longitudinal Study on Aging (aged 65-84).
One thousand fifty-two subjects (mean age+/-standard deviation = 71+/-5, 69% men) with normal MP at baseline.
Six tests (standing up from a chair, stepping up, tandem walk, standing on one leg, walking speed, and steps turning 180 degrees ) were used to assess MP at baseline and after 3 years. Baseline characteristics were potential predictors of MP decline.
Of the 1,052 subjects performing normally at baseline, 166 (15.8%) had declined in MP at follow-up. Older age, female sex, lower education, symptoms of distal symmetrical neuropathy, cognitive impairment without dementia, parkinsonism, heart failure, anemia, depressive symptoms, worse Mini-Mental State Examination score, and lost activities of daily living and instrumental activities of daily living (IADLs) were significantly associated with MP decline in univariate comparisons. Older age (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 2.14-6.88 comparing age classes > or =80 with 65-69), female sex (OR=1.50, 95% CI = 1.03-2.20), distal symmetric neuropathy (OR = 2.00, 95% CI = 1.03-3.87), depressive symptoms (OR = 1.85, 95% CI = 1.17-2.24), and baseline IADLs (OR = 1.22, 95% CI = 1.08-1.37 for each lost activity) independently predicted MP decline after regression analysis.
In a population-based cohort of elderly people with normal MP, one-sixth declined in 3 years. Age, sex, distal symmetrical neuropathy, depressive symptoms, and baseline IADLs independently predicted this decline. Distal symmetrical neuropathy is underestimated in the clinical and epidemiological evaluation of motor decline in older people.
Journal of the American Geriatrics Society 02/2006; 54(2):318-24. · 3.74 Impact Factor
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Leonardo Pantoni,
Anna Maria Basile, Giovanni Pracucci,
Kjell Asplund,
Julien Bogousslavsky,
Hugues Chabriat,
Timo Erkinjuntti,
Franz Fazekas,
José M Ferro,
Michael Hennerici,
John O'brien,
Philip Scheltens,
Marieke C Visser,
Lars-Olof Wahlund,
Gunhild Waldemar,
Anders Wallin,
Domenico Inzitari
[show abstract]
[hide abstract]
ABSTRACT: Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.
Neuroepidemiology 02/2005; 24(1-2):51-62. · 2.31 Impact Factor
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[show abstract]
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ABSTRACT: The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study.
In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale).
Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5+/-12.5 versus 69.2+/-12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values P<0.001). History of hypertension (P=0.007) and atrial fibrillation (P<0.001) were significantly more frequent in female stroke patients, as were coma (P<0.001), paralysis (P<0.001), aphasia (P=0.001), swallowing problems (P=0.005), and urinary incontinence (P<0.001) in the acute phase. Brain imaging, Doppler examination, echocardiogram, and angiography were significantly less frequently performed in female than male patients (all values P<0.001). The frequency of carotid surgery was also significantly lower in female patients (P<0.001). At the 3-month follow-up, after controlling for all baseline and clinical variables, female sex was a significant predictor of disability (odds ratio [OR], 1.41; 95% CI 1.10 to 1.81) and handicap (OR, 1.46; 95% CI 1.14 to 1.86). No significant gender effect was observed on 3-month survival.
Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.
Stroke 05/2003; 34(5):1114-9. · 5.73 Impact Factor
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[show abstract]
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ABSTRACT: Recent studies have suggested that previous infection may be a risk factor for ischemic stroke mainly in young and middle-aged patients. The present study sought to further investigate the association between recent inflammatory events (IE) and ischemic stroke without age restriction and to determine the role of recent IE in different ischemic stroke subtypes.
We performed a case-control study with 93 consecutive hospitalized stroke patients and 200 (107 hospital and 93 community) controls. Acute IE, both infective and non-infective, occurring in the previous 30 days were assessed using a standard questionnaire. The TOAST criteria were used for ischemic stroke subtypes classification.
Acute IE in the previous 30 and 7 days were significantly and independently associated with ischemic stroke (37/93 vs. 47/200; OR 2.23, 95% CI 1.26-3.96 and 17/93 vs.16/200; OR 2.45, 95% IC 1.11-5.39, respectively). Stratifying for stroke subtypes, acute IE significantly and independently increased the risk of atherothrombotic (OR 5.72, 95% CI 2.14-15.25) and cardioembolic stroke (OR 3.02, 95%CI 1.20-7.63).
Acute IE increase the risk of acute ischemic stroke of atherothrombotic and cardioembolic type independently of other predisposing factors. Implications for daily clinical practice, in relation to prevention and treatment of IE in patients at risk, have to be explored.
Cerebrovascular Diseases 02/2003; 15(3):215-21. · 2.72 Impact Factor
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ABSTRACT: It has been hypothesized that the use of different visual rating scales partly explains the discordant results of studies investigating risk factors and clinical correlates of age-related cerebral white matter changes (leukoaraiosis). We aimed to compare 6 widely used rating scales for leukoaraiosis and to calculate conversion coefficients of the score of 1 scale in the score of a second scale.
Two trained raters evaluated 80 pairs of CT and MRI scans using 2 CT and 4 MRI rating scales for white matter changes. Correlations among the scales were evaluated and regression lines were constructed with each of the CT and MRI scale scores as variables.
A high correlation was observed in all the paired comparisons of the 6 scales (Spearman's rho ranging from 0.85 to 0.96, P<0.0001). Using regression analysis, we determined numeric parameters to transform the score of 1 scale to the corresponding score for each of the remaining scales and relative confidence intervals. The predictive values of these conversions expressed as R(2) ranged from 0.75 to 0.92.
The present findings support the view that a good correlation exists among the considered visual rating scales for white matter changes. With the limitation that conversion parameters are calculated by applying a linear regression to partly nonlinear scales, their use allows comparison of the results of previous studies that used different scales and to pool data from past and ongoing clinical trials.
Stroke 12/2002; 33(12):2827-33. · 5.73 Impact Factor
