Alzheimer Disease: Staekenborg SS

Staekenborg SS, van der Flier WM, van Straaten EC, Lane R, Barkhof F, Scheltens P. · Department of Neurology and Alzheimer Centre, Vrije University Medical Centre, Amsterdam, The Netherlands. · Stroke. · Pubmed #18096841 links to  free full text

Abstract: BACKGROUND AND PURPOSE: The aim of this study was to describe the prevalence of a number of neurological signs in a large population of patients with vascular dementia (VaD) and to compare the relative frequency of specific neurological signs dependent on type of cerebrovascular disease. METHODS: Seven hundred six patients with VaD (NINDS-AIREN) were included from a large multicenter clinical trial (registration number NCT00099216). At baseline neurological examination, the presence of 16 neurological signs was assessed. Based on MRI, patients were classified as having large vessel VaD (18%; large territorial or strategical infarcts on MRI), small vessel VaD (74%; white matter hyperintensities [WMH], multiple lacunes, bilateral thalamic lesions on MRI), or a combination of both (8%). RESULTS: A median number of 4.5 signs per patient was presented (maximum 16). Reflex asymmetry was the most prevalent symptom (49%), hemianopia was most seldom presented (10%). Measures of small vessel disease were associated with an increased prevalence of dysarthria, dysphagia, parkinsonian gait disorder, rigidity, and hypokinesia and as well to hemimotor dysfunction. By contrast, in the presence of a cerebral infarct, aphasia, hemianopia, hemimotor dysfunction, hemisensory dysfunction, reflex asymmetry, and hemiplegic gait disorder were more often observed. CONCLUSIONS: The specific neurological signs demonstrated by patients with VaD differ according to type of imaged cerebrovascular disease. Even in people who meet restrictive VaD criteria, small vessel disease is often seen with more subtle signs, including extrapyramidal signs, whereas large vessel disease is more often related to lateralized sensorimotor changes and aphasia.

Staekenborg SS, Koedam EL, Henneman WJ, Stokman P, Barkhof F, Scheltens P, van der Flier WM. · Department of Neurology, Alzheimer Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Stroke. · Pubmed #19228848 No free full text.

Abstract: BACKGROUND AND PURPOSE: We sought to determine the predictive value of magnetic resonance imaging measures of vascular disease (white matter hyperintensities [WMHs], lacunes, microbleeds, and infarcts) compared with atrophy on the progression of mild cognitive impairment to dementia. METHODS: We included 152 consecutive patients with mild cognitive impairment. Baseline magnetic resonance imaging was used to determine the presence of medial temporal lobe atrophy and vascular disease (presence of lacunes, microbleeds, and infarcts was determined, and WMHs were rated on a semiquantitative scale). Patients were followed up for 2+/-1 years. RESULTS: Seventy-two (47%) patients progressed to dementia during follow-up. Of these, 56 (37%) patients were diagnosed with Alzheimer's disease, and 16 (10%) patients were diagnosed with a non-Alzheimer dementia (including vascular dementia, frontotemporal lobar degeneration, and Parkinson dementia). Converters were older and had a lower Mini-Mental State Examination score at baseline. On baseline magnetic resonance imaging, patients who progressed to a non-Alzheimer dementia showed more severe WMHs and had a higher prevalence of lacunes in the basal ganglia and microbleeds compared with nonconverters. Cox proportional-hazard models showed that, adjusted for age and sex, baseline medial temporal lobe atrophy (hazard ratio=2.9; 95% CI, 1.7 to 5.3), but not vascular disease, was associated with progression to Alzheimer's disease. By contrast, deep WMHs (hazard ratio=5.7; 95% CI, 1.2 to 26.7) and periventricular hyperintensities (hazard ratio=6.5; 95% CI, 1.4 to 29.8) predicted progression to non-Alzheimer dementia. Furthermore, microbleeds (hazard ratio=2.6; 95% CI, 0.9 to 7.5) yielded a >2-fold increased, though nonsignificant, risk of non-Alzheimer dementia. CONCLUSIONS: Medial temporal lobe atrophy and markers of cerebrovascular disease predict the development of different types of dementia in mild cognitive impairment patients.

Staekenborg SS, van Straaten EC, van der Flier WM, Lane R, Barkhof F, Scheltens P. · Dept. of Neurology and Alzheimer Centre, Vrije Universiteit Medical Centre, 7057, 1007 MB Amsterdam, The Netherlands. · J Neurol. · Pubmed #18677637 No free full text.

Abstract: OBJECTIVE: The aim of this study was a cross-sectional comparison of clinical and MRI characteristics and risk factor profiles between patients with small vessel disease (lacunae and white matter hyperintensities) and large vessel disease (large territorial or strategical infarcts) in a large cohort of VaD patients. METHODS: Patients with VaD (NINDS-AIREN) were included in a large multicenter treatment trial (the VantagE study). All patients were examined by a neurologist and interviewed about their medical history. Based on MRI, patients were classified as having large vessel VaD, small vessel VaD, or a combination. Other MRI characteristics included white matter hyperintensities (WMH), medial temporal lobe atrophy (MTA) and general cortical atrophy. RESULTS: Of the 706 patients, 522 (74 %) had small vessel disease, 126 (18 %) had large vessel disease and 58 (8 %) had both. Patients with small vessel disease were older and less educated, and showed more cortical and medial temporal lobe atrophy than patients with large vessel disease. The most prevalent vascular risk factors (hypertension, diabetes and smoking) were equally distributed between the different types of VaD. However, patients with large vessel disease had more hypercholesterolemia and cardiac risk factors compared to patients with small vessel disease. CONCLUSION: Cerebrovascular disease underlying VaD consists in the majority of small vessel disease and in about one fifth of large vessel disease. This study demonstrates heterogeneity between these two groups with regard to risk factor profile and atrophy scores on MRI.

Bastos-Leite AJ, van der Flier WM, van Straaten EC, Staekenborg SS, Scheltens P, Barkhof F. · Image Analysis Center, VU University Medical Center, Amsterdam, The Netherlands. · Stroke. · Pubmed #17962598 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Besides cerebrovascular disease, medial temporal lobe atrophy (MTA), a neuroimaging finding suggestive of degenerative pathology, has been shown in vascular dementia (VaD). However, it is unknown to what extent MTA contributes to the pattern of cognitive impairment observed in VaD. Therefore, our purpose was to investigate the relative contribution of cerebrovascular disease and MTA to cognitive impairment in patients fulfilling diagnostic criteria for VaD. METHODS: We examined 590 patients (374 men; mean age, 73 years; standard deviation, 8) with probable VaD according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria at inclusion into a multicenter clinical trial. Cerebrovascular disease and the degree of MTA were evaluated by using MRI. Cognitive testing included the Mini-Mental State Examination, and the vascular dementia assessment scale. RESULTS: On the basis of the operational definitions for the neuroimaging part of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, 485 (82.2%) patients had small vessel VaD and 153 (25.9%) had large vessel VaD. More than half (59.8%) of the patients had considerable MTA. Multiple linear regression analyses revealed that after correction for sex, age, education, and duration of dementia, neuropsychological tests showed that patients with higher grades of MTA or large vessel VaD had significantly worse general cognitive and executive functioning, whereas associations with small vessel disease were restricted to worse executive functioning. CONCLUSIONS: Both MTA and large vessel disease contribute to global cognitive impairment in VaD. Small vessel disease contributes to executive dysfunction.

Staekenborg SS, Gillissen F, Romkes R, Pijnenburg YA, Barkhof F, Scheltens P, van der Flier WM. · Alzheimer Centre and Department of Neurology, Vrije Universiteit Medical Centre, Amsterdam, the Netherlands. · Int J Geriatr Psychiatry. · Pubmed #17907266 No free full text.

Abstract: BACKGROUND: The neuropathology of behavioural and psychological symptoms is much less understood than the neuropathology of cognitive impairment in AD. On MRI, medial temporal lobe atrophy (MTA) is presumed to reflect Alzheimer- type pathology. White matter hyperintensities (WMH) are considered markers of vascular pathology. AIM: We investigated differences in prevalence of behavioural and psychological symptoms in AD according to the presence of MTA and WMH on MRI. METHODS: Behavioural and psychological symptoms of 111 consecutive AD patients were assessed using the Neuropsychatric Inventory (NPI). Symptoms were considered present when the score was > or =1. On MRI, MTA was rated using the five-point Scheltens-scale and WMH using the four-point Fazekas-scale. Both MRI measures were dichotomised (MTA: absent 0/1, present 2-4; WMH absent 0/1, present 2/3). RESULTS: Of the 111 AD patients, 60(55%) had MTA, and 32(29%) had WMH. The presence of MTA was associated with the presence of WMH (chi (2) = 11.8, p < 0.001). The prevalence of behavioural and psychological symptoms--defined as a NPI score of > or =1 on at least one symptom--was 74%.The median NPI score of the total study population was 6(0-41). There was no difference in prevalence according to MTA (p = 0.53) or WMH (p = 0.18). On inspection of individual NPI items, neither MTA, nor WMH was related to any of the symptoms. CONCLUSIONS: There were no differences in prevalence of behavioural and psychological symptoms according to MTA or WMH, as rated on MRI. This suggests that the occurrence of those symptoms depends on other determinants, such as coping style or genetic make-up.