Vascular risk factors and intensity of cognitive dysfunction in MCI

Journal of the Neurological Sciences 257 (2007) 202 – 205 www.elsevier.com/locate/jns

Vascular risk factors and intensity of cognitive dysfunction in MCI Joanna Siuda ⁎, Agnieszka Gorzkowska, Grzegorz Opala, Stanisław Ochudło Department of Neurology, Aging, Vascular and Neurodegenerative Diseases, Silesian Medical University, Central University Hospital, ul. Medyków 14, 40–752 Katowice, Poland Available online 1 March 2007

Abstract Patients with Mild Cognitive Impairment (MCI) have a greater risk of developing dementia than general population. Lots of evidence suggests that cardiovascular risk factors appear more often in the MCI than in general population The aim of this study was to evaluate association between cardiovascular risk factors and intensity of cognitive impairment in MCI patients. We evaluated 24 MCI patients (9 women and 15 men) fulfilling Mayo Clinic Group Criteria. Taking under consideration presence of cardiovascular diseases patients were divided into two groups: first group (n = 16) MCI with cardiovascular diseases and second group (n = 8) MCI without cardiovascular disorders. Cognitive functions were assessed by neuropsychological tests battery including MMSE, Clock Drawing Test, Trail Making Test (TMT), Verbal Fluency Test with letters FAS, Auditory Verbal Learning Test (AVLT). In the MCI group with vascular risk factors we have found more distinct dysfunction of learning new information, recall and short-term memory than in MCI patients without vascular pathology. In conclusion we may suggest that more distinct cognitive deficit may indicate higher risk of developing dementia, that is why patients with MCI should be under special supervision, with at least annual neuropsychological evaluation. © 2007 Elsevier B.V. All rights reserved. Keywords: Mild Cognitive Impairment; Vascular risk factors; Cognition; Neuropsychological assessment; Dementia; Cardiovascular diseases

1. Introduction World population is growing older. It is estimated that European elderly population will reach over 20% in the second half of XXI century. One of the most common complaints in the elderly patients is cognitive impairment, mainly poor memory. By now, we are quite accurate in diagnosing dementia. Nowadays major research effort is to develop strategies to prevent or at least delay dementia onset. The identification of people with increased risk of developing dementia is the first step. In 1999 Mayo Clinic Group proposed a new conception — Mild Cognitive Impairment (MCI), placing it between normal ageing and dementia. MCI is characterised by cognitive impairment no dementia, estimated and proved in psychological tests, confirmed by family doctor and/or family members, but without influence on activities of daily living [1]. Patients with Mild Cognitive Impairment have a greater risk of de-

⁎ Corresponding author. Fax: +48 32 204 61 64. E-mail address: [email protected] (J. Siuda). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.01.034

veloping dementia than general population [2]. Cognitive dysfunction found in this group will progress into dementia in about 10%–12% of cases within a year and this number is growing each year [3–6]. In the MCI group we are still looking for factors allowing estimating the risk of developing dementia. Early identification of various forms of predementia syndrome is important because it could lead to early specific pharmacological or rehabilitation interventions. There are some data suggesting that vascular pathology plays an important role in pathogenesis of primary neurodegenerative dementia such as Alzheimer's disease and in other dementia [5]. Lots of evidence suggests that cardiovascular risk factors appear more often in the MCI than in general population [5–9]. It is reasonable to postulate that the presence of vascular disorders would contribute the intensity of cognitive impairment in the MCI group. On the other hand, some previous researches indicated less probability of progression of cognitive pathology in MCI patients group with White Matter Lesion's (WML's) [10,11]. According to some literature data, vascular pathology in MCI may be associated with different and more stable cognitive deterioration profile [10,11].

J. Siuda et al. / Journal of the Neurological Sciences 257 (2007) 202–205 Table 1 Demographic data Group I with vascular risk factors

Group II without vascular risk factors

Mild Cognitive Impairment Number of patients (women/men) Age (± SD) Education (in years) (±SD)

16 (7/9)

8(2/6)

70.94 (±4.85) 72.13 (± 4.36) 13.81 (±3.97) 15.25 (± 3.41) Cardiovascular diseases

Arterial hypertension Ischemic heart disease Diabetes mellitus

62.5% (10 patients) 0% 62.5% (10 patients) 6.25% (1 patient) Pathology on CT scanning

Cerebrovascular changes Cortical atrophy

50% (8 patients) 62.5% (10 patients) Other risk factors

25% (2 patients) 87.5% (7 patients)

Hyperlipidemia Cigarette smoking

75% (12 patients) 50% (8 patients)

75% (6 patients) 25% (2 patients)

The aim of this study was to evaluate association between cardiovascular risk factors and intensity of cognitive impairment estimated in neuropsychological tests in patients with Mild Cognitive Impairment. 2. Materials and methods 24 MCI patients (9 women and 15 men) fulfilling Mayo Clinic Group Criteria [1] entered into this study. Data about cardiovascular risk factors, including: arterial hypertension, ischemic heart disease or arrhythmia, diabetes mellitus, hyperlipidemia, cigarette smoking and obesity, were assessed from patient's and informant medical review as well as from actual clinical evaluation. Taking under consideration presence of cardiovascular diseases patients were than divided into two groups: first group of 16 patients (7 women and 9 men) with MCI and cardiovascular diseases and second group of 8 patients (2 women and 6 men) with MCI without cardiovascular disorders. In both isolated groups the same percentage (75%) of patients had hyperlipidemia. 50% of patients in the first and 25% in the second group were smokers (up to 20 cigarettes a day). Every patient in both groups was well educated, mean education time was similar in both groups and it was respectively 13.81 and 15.25 years, everyone in those groups were retired. Mean age was 70.94 years in MCI group with concomitant vascular risk factors and 72.13 years in MCI group without those risk factors and it does not differ statistically. In the first group 10 patients (62.5%) had arterial hypertension, 10 patients (62.5%) had ischemic heart disease and 1 patient (6.25%) had diabetes. All demographic data are shown in Table 1. Cognitive functions were assessed by neuropsychological tests battery including MMSE, Clock Drawing Test, Trail Making Test (TMT), Verbal Fluency Test with letters FAS, Auditory Verbal Learning Test (AVLT). MMSE is a short (5–10 min) screening test to assess cognitive

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impairment, which consists of 5 areas: orientation, registration, attention and calculation, recall, language. The Clock Drawing Task tests executive ability and is sensitive to early cognitive impairment. The subject was asked to draw a clock with all the numbers on it and to set the time to 10 past 11. Trail Making Test assesses working memory capacity. The object of the test is for the subject to connect the numbers in order, beginning with 1 and ending with 25, in as little time as possible. Part B is more complex than A because it requires the subject to connect numbers and letters in an alternating pattern (1A–2–B–3–C, etc.) in as little time as possible. Word fluency is sensitive to early changes in cognitive function. In the Verbal Fluency Task, the subject was asked to say as many words as possible beginning with the letters “F” “A” “S” — each in 1 min. Verbal memory function was assessed by means of the Rey's Auditory Verbal Learning Test (AVLT), which consists of a list of 15 words that has to be remembered in 5 consecutive learning trials. After each presentation, the patient is prompted to recall as many words as he or she can remember from that list immediately and then after 30 min. Statistical analyses were conducted using a statistical software package. The groups comparisons were considered statistically significant if p b .05. To estimate the degree of impairment in patients, standardised z scores were calculated based on the mean and SD scores of the neuropsychological test battery administered to two MCI groups. This research received approval by the Ethics Comity in our institution, and informed consent was obtained from each patient. 3. Results A diagnosis of MCI was made if the patient meets all of the standard MCI criteria [12–14]. In neuropsychological assessment all patients had abnormal scores of memory test but not sufficient to diagnosis AD. MMSE was comparable in both groups (I group — 26.69 ± 1.9, II group — 26.89 ± 1.36). In the MCI group with vascular risk factors we have found more distinct dysfunction of learning new information, recall and short-term memory than in MCI patients without vascular pathology assessed by Auditory Verbal Learning Test — I group — 26.63 ± 6.23(total words), II group — Table 2 Results in neuropsychological assessment battery Neuropsychological tests mean values (±SD)

Mild Cognitive Impairment Group I with Group II without vascular pathology vascular pathology

MMSE (points) 26.69 (±1,88) 26.87 (± 1.35) Clock Drawing Test made correctly in both groups AVLT (number of words) 26.62 (±6.22)⁎ 29.75 (± 4.23) AVLT30 (number of words) 4.37 (±2.18) 5.62 (± 2.61) Verbal fluency (number of words) 26 (±6.88) 24.25 (± 8.54) TMT A (time in seconds) 68.81 (±18.4) 61.25 (± 21.0) TMT B (time in seconds) 169.87 (±53.5) 154.62 (± 72.13) ⁎p b 0.1.

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29.75 ± 4.23(total words), after 30 min — I group — 4.37 ± 2.19 (words), II group — 5.63 ± 2.62 (words). Working memory capacity assessed by Trail Making Test part A — I group — 68.81 ± 18.48 (s), II group — 61.25 ± 21.07(s) and after Trail Making Test part B — I group — 169 ± 53.51(s), II group — 154.63 ± 57.31(s) (Table 2). 4. Discussion There are many literature data pointing out influence of cardiovascular risk factors on incidence and progression of dementia [5–9,12]. The researches, including vascular dementia and primary neurodegenerative diseases such Alzheimer disease, proved the role of vascular risk factors in prevalence of cognitive impairment. Population based Rotterdam Study has shown coexistence of micro- and macroangiopathy with vascular and Alzheimer dementia [13,15]. Ischemic heart disease, especially arterial fibrillation is often found in cognitively impaired subject. Atheromatosis found in ischemic heart disease is usually coexisted with cerebrovascular disease and it is elevating 3 to 10 times the appearance of neurodegenerative changes characteristic for Alzheimer disease. Arterial hypertension was also examined as a potential risk factor for dementia. It is now known as the strongest risk factors for vascular dementia. Many reports in the literature are pointing out that midlife hypertension even if well medicated plays an important role in elderly cognitive impairment [16–18]. In the Framingham Study hypertension and obesity was found to have independent influence on cognitive impairment [17,18]. These researches differ from Maruyama et al. studies, where MCI no progress patients showed higher levels of white matter lesions. The authors suggested that MCI with vascular pathology may be a brain ageing form and may have nonamnestic cognitive deterioration profile [18,19]. In contrast to this study we identified in our comparable patients group amnestic type of cognitive deterioration. Additionally short memory deficit was more intensive then in MCI patients without vascular risk factors. Cigarette smoking was also examined in demented subject as a potential risk factor, but its role in pathogenesis of cognitive impairment still remains unclear [12]. Revelation of its protective role was not proven. In our group of patients with MCI presence of cardiovascular factors were over 60%. It is in agreement with the majority of studies showing that cardiovascular risk factors are common in this group. It is now well recognised that cognitive impairment in old age is associated with brain disturbances rather than ageing per se. Neuropathological cascade leading to cognitive impairment and dementia starts decades before the clinical manifestation and thus identification of risk factors earlier in life may be of importance for modification of disease processes. There are many mechanisms that account for the association between vascular risk factors and cognition, but at the moment precise mechanisms remain unknown. There are only a few studies examining incidence of MCI. Italian researches found no relation

between age, education and sex and prevalence of MCI [20]. Other studies reported higher prevalence rates for lower level of education. In our study MMSE score was similar in both groups. It was mainly used to exclude patients with dementia from MCI. We think that using this test for evaluation patients with mild cognitive impairment is not enough, especially if you have patients with high education level. Larger neuropsychological test battery must be used to recognise patients with mild to moderate cognitive impairment no dementia [21,22]. Our results demonstrate the predominant memory impairment is not only a characteristic feature for MCI patients group but also a factor, which can distinguish MCI subgroups. Based on our results, we may say that cardiovascular risk factors not only predisposed to cognitive impairment but also have an influence on it intensity. Vascular risk factors represent common and modifiable risk factors, its early identification and than effective control may lead to lower the risk of late-life cognitive impairment and dementia. 5. Conclusions 1. In our MCI group with vascular risk factors more intensive dysfunction in learning ability, short-term memory, and delay recall and operation memory was found then in the MCI group without vascular pathology. 2. More distinct cognitive deficit may indicate higher risk of developing dementia. 3. Patients with Mild Cognitive Impairment should be under special supervision, with at least annual neuropsychological evaluation. References [1] Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterisation and outcome. Arch Neurol 1999;56:303–8. [2] Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, et al. Mild cognitive impairment represents early-stage Alzheimer's disease. Arch Neurol 2001;58: 397–405. [3] Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133–42. [4] Petersen RC, Doody R, Kurz A, Moth RC, Morris JC, Rabins PV, et al. Current concept in mild cognitive decline. Arch Neurol 2001;58:1985–92. [5] Solfrizzi V, Panza F, Colacicco AM, D'Introno A, Capurso C, Torres F, et al. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882–91. [6] Morris J. Mild Cognitive Impairment and Preclinical Alzheimer's Disease. Geriatrics Jun 2005:9–14. [7] Yener GG, Ozturk V, Uzunel F, Aydin H, Baklan B. Diagnosis profile and comparison of risk factors in major types of dementia: a hospital base study. J Neurol Sci 2004;21:301–10. [8] Kivipelto M, Helkala T, Hanninen T, Laakso MP, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and late-life mild cognitive impairment — a population base study. Neurology 2001;56:2. [9] Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, et al. ApoE4allele, elevated midlife cholesterol level and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Annals Intern Med 2002;137:3.

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