Casebook of Clinical Neuropsychology Edited by Joel E. Morgan Ida Sue Baron Joseph H. Ricker OXFORD 2011TRS re pereneeree | i ' i 60 Vascular Dementia Nikki H. Stricker, Joseph R. Sadek, and Kathleen Y, Haaland ‘Vascular dementia is the second leading cause of dementia in the elderly following Alzheimer’s disease. Prevalence estimates in pathologic stud- ios suggest that vascular dementia accounts for roughly 11% of dementia cases (Jellinger, 2008), with clinical estimates ranging from 4.5% to 39% (Kase, 1991). Prevalence estimates vary widely due to the heterogeneous nature of vascular dementia, sampling bias, the high prevalence of mixed neuropathology, and the existence of multiple classification systems (DSM, ICD-10, NINDS-AIREN, ADDTC; see Haaland & Swanda, 2008 for review) that are not inter- changeable (Gold et al., 2002). Multiple mecha- nisms of cerebrovascular disease can have differing clinical presentations, and several subtypes of vascular dementia have been pro posed (Erkinjuntti, 2007), including strategic infarct dementia (see Roman et al., 1993), sub- cortical vascular dementia (also known as small- vessel dementia or subcortical ischemic vascular dementia), and multi-infarct dementia (also known as cortical vascular dementia or post- stroke dementia) Multi-infarct dementia (Hachinski, Lassen, & Marshall, 1974) is often viewed as the prototypi- cal vascular dementia syndrome, characterized by multiple cortical or subcortical infarcts that can be visualized by neuroimaging, sudden onset of symptoms with stepwise progressive deterio- ration, focal neurologic signs, and neuropsycho- logical deficits that are related to specific sites of damage. The cognitive deficits associated with multi-infarct dementia are fairly heterogeneous, 642 depending on lesion location, Although histori- cal views of vascular dementia were based on multi-infarct dementia, itis now recognized that cognitive deficits associated with cerebrovascu- lar disease are rouch broader than that captured by multi-infarct dementia, Although multi-in- farct dementia is ofien considered the type of vascular dementia most frequently encountered by neuropsychologists (Lezak, Howieson, & Loring, 2004), and as such was chosen for the current case study, this may not be the case A recent magnetic resonance imaging (MRI) study revealed that subcortical vascular demen- tia, specifically small-vessel vascular dementia, accounted for 74% of 706 vascular dementia cases based on DSM-IV and NINDS-AIREN criteria, MRI, and neurological and neuropsy- chological evaluation (Staekenborg et al, 2008), although without neuropathological data it cannot be determined whether additional early Alzheimer pathology may also have contributed. “the cognitive and behavioral changes in sub- cortical vascular dementia are more homoge- neous than those in multi-infarct dementia due to their association with a particularly signifi- cant disruption of prefrontal-subcortical circ ‘These changes are often more insidious and are characterized by predominant executive dys- function, psychomotor slowing, and changes in gait, urinary functioning, affect, and mood (see Roman, Erkinjuntti, Wallin, Pantoni, & Chui, 2002 for review). Clinically significant deficits associated with cerebrovascular mecha- nisms often do not meet traditional criteria for igi eee bee ate penn)' Vascular Dementia dementia, For example, the DSM-IV requires cognitive impairment in two or more domains, one of which must be memory. Such tradi- tional dementia criteria are largely based on the clinical presentation of Alzheimer’s disease, wherein the hallmark symptom is early memory impairment. Only one of the previously men- tioned dementia classification symptoms (ADTTC; Chui et al., 1992) does not require memory impairment for a diagnosis of vascular dementia, although multiple researchers have argued against the memory criteria (Benisty et al., 2008; Bowler, 2003; Hachinski et al, 2006; Roman et al., 2004). Alternatives to the highly debatable term “vascular dementia,” such as vascular cognitive impairment (VCI; Hachinski, 1994) and vascu- lar cognitive disorder (VCD; Sachdev, 1999; see O'Brien et al., 2003 for review), have been proposed in an effort to capture a wider range of cognitive impairment resulting from various causes of cerebrovascular disease and to allow for early identification of this impairment (Bowler, 2002). There are a multitude of vascular risk factors that are associated with vascular cog- nitive impairment, including arterial hyperten. sion, diabetes, hypercholesterolemia, history of stroke or transient ischemic attack, smoking, atrial fibrillation, myocardial infarction, coro- nary heart disease, and generalized atherosclero- sis (Erkinjuntti, 2007; Roman et al., 2004). It has been shown that vascular risk factors also increase one’s risk of developing Alzheimer’s dis- ease (Jin, Ostbye, Peightner, Di Legge, & Hachin- ski, 2008) and some researchers have argued that vascular dementia and Alzheimer’s disease may share a common etiology (Casserly & Topol, 2004; de la Torre, 2002; Zlokovic, 2004). ‘The dif. ferential diagnosis of vascular dementia from Alzheimer’s disease is often part of the neurop- sychological referral question. This distinction can be difficult and is confounded by the high prevalence of co-occurring vascular and Alzheimer neuropathology (see Jellinger & Attems, 2007 for review). Several studies have suggested that whereas episodic memory impair- ‘ment is the most significant cognitive deficit in Alzheimer’s disease, greater executive dysfunc- tion relative to other cognitive domains is the hallmark of vascular dementia (Desmond, 2004; Graham, Emery, & Hodges, 2004), although 643 some studies do not support the specificity of executive dysfunction (Reed et al,, 2007). The following case study was selected because it exemplifies a multi-infarct dementia, with MRI evidence of both cortical and subcortical involvement that corresponds to the patient’s clinical presentation. Case Study ‘The patient is a 58-year-old, left-handed, single, Caucasian male with 12 years of education anda history of multiple strokes (1973, 2006). He has never been married, has no children, denied any history of learning disability, and worked in a medical facility for 40 years, most recently in medical records. He was referred by-his physi- cian because the family and attorney had con- cerns that the patients cognitive deficits had resulted in bankruptcy. ‘The history was obtained from the patient, his sister, ard hospital records. The patient had two cerebrovascular accidents that required hospi- talization. ‘The first in 1973 was associated with persisting deficits in peripheral vision, and impairment in speed of processing, divided attention and switching tasks, and topographic orientation. The second in 2006 was reportedly associated with additional persisting deficits that included left homonymous hemianopsia, decreased sensory perception on the right side of the body, spastic gait, additional psychomotor slowing, bradykinesia, slurred speech, decreased writing legibility, and decreased short-term memory, There was urinary incontinence and retention following the stroke that partially resolved. His most recent neurological exam also noted hyperreflexia and mildly increased tone in the patient’s extremities, ‘These deficits negatively affected his ability to function at his job and he subsequently retired. ‘An MRI of the brain (see Figure 60-1) 2 days following the 2006 stroke revealed moderate dif- fuse cerebral volume loss, multiple bilateral infarcts in the occipital and frontal lobes, left cerebellar infarct, small lacunar infarcts in the left putamen and bilateral thalami, and mild to moderate periventricular white matter changes. In addition, diffusion weighted images showed punctate areas of restricted diffusion on the periphery of the left occipital infarct consistentEc 644 BY Vascular Disorders Figure 60-1. Magnetic resonance imaging, (Top row) Axial slices of fuid-attenuated inversion recovery (FLAIR) sequence that is complicated by motion artifact. (Bottom row) Axial slices of T2-weighted sequence. with new small areas of infarction, located at the posterior temporal occipital junction. The patient reported that he was currently filing for bankruptcy due to outstanding credit card debt and loss of his job following the 2006 stroke, The patient’ sister has had durable power of attorney for his finances since that time. Although the patient reported some decrease in function, he did not seem to appreciate the full significance of his deficits. He lives alone and reported no functional impairment except that he has not driven since the last stroke. ‘The patient’ sister, however, reported impairments in several instrumental activities of daily living (eg, finances, cooking, shopping). Other medical history included a 40-year his tory of hypertension and one pack per day of ciga rette smoking, a remote history of heavy alcohol use, and a strong family history of vascular risk fee tors, induding congenital heart problems and factor V Leiden deficiency (genetic disorder that kof blood clots). The patient scored 12 out ofa possible 13 points on Rosen's modifica- tion of the Hachinski Ischemic Score (HIS; Rosen, Tetry, Fuld, Katzman, & Peck, 1980) due to the presence of the following characteristics: abrupt increases the ri onset, “stepwise” decline, somatic complaints, hypertension history, stroke history, focal neuro logical symptoms, and focal neurological signs Even on this briefer ischemic scale, the patient’s score is well above the suggested 7-point cut-off suggestive of multi-infarct dementia based on Hachinskis original scale. The patient denied any significant psychiatric history. Medications included Finasteride (5 mg) and Tamsulosin (0.4 mg) daily for benign hypertrophy of the pros- tate, Hydrochlorothiazide (25 mg) and Metoprolol (25 mg daily) for hypertension, and Warfarin (8 mg daily) for thrombosis prevention. ‘The patient was pleasant, responsive to ques- tioning, and he cooperated with all aspects of the evaluation, He ambulated with the assistance of a walker but could move withoutit when needed. He exhibited occasional word-finding difficulty, and his speech was slow and dysarthric, but of normal volume and prosody. He demonstrated good attention, understood test instructions, and appeared to put forth adequate effort. His response latency was slow. His affect was full ange, stable, and consistent with euthymic mood. ‘The neuropsychological evaluation wes considered valid. aren secant aneR sennai Vascular Dementia Test Results Please refer to Table 60-1 for raw scores and nor- mative test data. Estimated premorbid inteli- gence (Shipley) and simple auditory attention were in the average range. Working memory was impaired as evidenced by his inability to perform more than two digits backward and missing two calculations on serial sevens. He showed slight evidence for left hemifield neglect on line bisec- tion, although he seemed to adequately compen- sate for this on other tasks, Although his slowed motor speed, visual field cut and possible neglect likely contributed to his moderately to severely impaired performance on two psychomotor tasks 645, (Trails A and Digit Symbol), his slowness in reciting familiar sequences and his long response latencies throughout the exam suggest that he has deficits in processing speed that cannot be explained by motor or visual impairment, Learning and memory skills were character- ized by mildly impaired encoding and retrieval without evidence of rapid forgetting. On a word list learning task (CVLT-ID), he recalled 4/16 words on trial 1 (mildly impaired, ~1.5 SD) and 10/16 words by trial 5 (average range, -0.5 SD). Short- and long-delay free recall were within the average range (8/16 and 7/16 words, respec- tively), and he did not benefit from cues. He showed poor self-monitoring across the learning Table 60-1, Neuropsychological Test Scores (Raw and Normative Values) Cognitive Domain/Test Raw Score Normative Score General Cognition Estimated Premorbid Intellectual Functioning Shipley Institute of Living Scale Vocabulary 28 48T Abstraction 2 467 Estimated WAIS-R IQ = 102 Screening Measure ‘Mini Mental Status Exam. 5 Attention / Working Memory / Processing Speed Digit Span (WAIS-II1) n 788 Longest digit span forwards 6 68 cum% Longest digit span backwards 2 98.5 cum Digit Symbol Coding (WAIS-IL]) 9 28s ‘Mental Control (WMS-IHf) B 5S ‘Trail-Making Test Part A 27 MT Line Bisection Memory California Verbal Learning ‘Test-Second edition Learning! Acquisition (Trials 1-5 Total) ‘Trial 1 ‘Trial 5 List B Short-delay Free Recall Short-delay Cued Recall Long-delay Free Recall Long-delay Cued Recall ‘Total Recognition Discriminability Rey-Osterreith Complex Figure Test Immediate Recall slight evidence for left hemifield neglect 34 4oT 4 -157 10 052 3 152 8 052 6 152 7 05% 6 15x 18 107 05 <0 (Continued)Vascular Disorders Table 60-1, Neuropsychological Test Scores (Raw and Normative Values) (Continued) (Cognitive Domain/Test Raw Score Normative Score Language Letter Fluency (FAS) a 2T Semantic Fluency (animals) 16 OT Boston Naming Test SI aT Perceptual Errors 3 Constructional and Visuospatial Abilities Rey-Osterreith Complex Figure Test Copy 0s 300 BT Sensory/Perceptual Skills Visual Field Errors Right visual field 0/24 ‘ Left visual field 17124 Tactile Finger Recognition Errors Dominant Left Hand 12/20 Nondominant Right Hand 12720 Finger Tip Writing Errors Dominant Left Hand 9120 Nondominant Right Hand 6120 Motor Skills Halstead-Reitan Finger Tapping Dominant Left Hand 184 oT Nondominant Right Hand 2 RT Grooved Pegboard Dominant Left Hand 193 IT Nondominant Right Hand unable to perform Emotional Functioning Beck Depression Inventor 1 WAIS-R, Wechsler Adult Intelligence Scale-Revisedh WAIST, Wechsler Adu Intelligence Scale~Third revision; WMS-IIL, ‘Wechsler Memory Scale-Thitd revision and recall trials, with an excessive number of intrusions (12 intrusions, 1.5 $D). His perfor- ‘mance on yes/no recognition was within the low average range, consistent with his recall perfor- mance. His recall of a complex design after 43-minute delay was qualitatively similar to his copy, suggesting that he was able to retain the Timited amount of material he encoded initially (both ‘were similarly distorted and impaired as will be discussed later). Language skills were generally intact for con- frontation naming, and there was also no obvi- us difficulty with language comprehension. The Patient’ performance was mildly to moderately lampaired on a task that required rapid genera- tion of words within phonetic categories, likely ON ee nai PE rl esr = eeers nr Vascular Dementia due to executive dysfunction (ie., impaired ini- tiation). His performance improved to the low average range when asked to rapidly generate words within a semantic category. ‘The patient showed marked deficits in visu- ospatial skills due to impaired organization and planning rather than frank spatial deficits. Per- ception of line orientations and his ability to copy simple figures were largely intact, but his ability to copya highly complex geometric design was severely impaired (see Figure 60.2; see also the color figure in the color insert section). His approach was disorganized and piecemeal. He drew a distorted outline of the figure and did not appear to appreciate the gestalt. He drew some of the details of the design, but they were distorted and misplaced. He also showed moderately impaired performance on block constructions and when asked to integrate cut-up objects and perceive how the pieces fit together (Hooper Visual Organization Test). He frequently focused on one detail of the cut-up object without inte- grating the rest of the pieces. For example, he per- ceived a cup as a purse, likely because he focused on the cup handle, and he perceived a table asa shelf because he failed to integrate the legs. There was other clear evidence of executive dysfunction, including difficulty with flexibility of thinking, problem-solving skills, ability to respond to feedback, perseverative responding, and sequencing. He committed a high number of errors and perseverative responses on a card- sorting task (WCST-64) indicative of difficulty Copy Order: hme 647 developing solutions to the task, shifting between target sets learning from previous mistakes, sef- monitoring, anti verbal control of his behavior. For example, he continued to perseverate to form even though he verbalized that the current prin- ciple was color. Although he demonstrated impairment on a test requiring rapid alternation between numbers and letters (Trails B), he did not make any errors and he was similarly slow on a numeric sequencing task that did not require alternation (Trails A), As noted previously, his ability to rapidly generate words beginning with a target letter was mildly to moderately impaired and his ability to copy a complex figure was severely impaired, consistent with an overall pat- tem of disorganization and inefficient planning, Fine motor dexterity (Grooved Pegboard) and simple motor speed (Finger Tapping) were severely impaired bilaterally, especially in the right nondominant hand for dexterity. Sensory perceptual testing confirmed his left visual field cut. He had difficulty distinguishing between his fingers bilaterally on a test of tactile finger recog- nition (finger agnosia), and there was evidence of graphesthesia bilaterally. The patient’ finger agnosia and graphesthesia may be related to old thalamic infarcts in the absence of left parietal involvement, but the presence of diffuse damage makes any precise neuroanatomical correlates difficult Self-report was indicative of mild depression, but the symptoms he endorsed were related to physical changes from stroke, such as low energy Figure 60-2. Patient’ copy of the Rey-Osterreith Complex Figure with the target stimulus in the top right corner.648 and physical barriers to activities, Therefore, depression did not appear to significantly con- tribute to his impaired performance. Discussion This patients performance on neuropsychologi- cal evaluation was in the moderately impaired range overall, which represented a decline from his estimated average premorbid level of func- tioning, While his language, simple spatial skills, and learning and memory skills were largely intact, he demonstrated deficits that were consis- tent with his history of multiple bilateral strokes and periventricular white matter abnormalities, His neuropsychological profile was character- ized by (1) greatest impairment in executive functions, including lack of awareness of his def- ‘cits, impaired working memory, perseverative responding, impaired flexible problem solving, spatial organization, rapid word generation, sequencing and speed of information process- ing, which were consistent with documented infarcts, lacunes, and periventricular white matter changes, (2) mildly impaired encoding and retrieval without evidence of rapid forgetting, (3) bilateral motor deficits, worse on the right, and (4) functional impairment. The patients MMSE score of 25 was not in the impaired range. Because this widely used screening measure is relatively insensitive to executive dysfunction, it frequently overestimates the patient’s general level of cognitive functioning when executive deficits are predominant, It is often helpful to Point this out in clinical reports for the benefit of other providers. ‘The referral question of whether his cognitive status may have contributed to his debt accrual cannot be confidently answered because his debt ‘was acquired prior to the 2006 stroke and one cannot reliably conclude what his cognitive abilities and functional capacities were during that period, although subcortical white matter changes that accumulate gradually over time may have contributed, The patient’s marked deficit in executive functions and his lack of insight into his deficits suggest that he currently does not have the capacity to make financial decisions, and it is appropriate that his sister continue to manage his finances and retain Vascular Disorders power of attorney, The sister’ participation in medical appointments was encouraged to help the patient remember and implement any medical recommendations, This patients clinical presentation is consis- tent with a diagnosis of vascular dementia, Firs, he has multiple vascular risk factors and a his. tory of two frank strokes, There is documented MRI evidence of these events, other silent infarcts, and microvascular ischemic disease, Second, his neuropsychological profile is consis. tent with these vascular insults, particularly the subcortical involvement, with relatively greater impairments in executive function, attention and psychomotor speed relative to his largely intact language, simple spatial skills, and ‘memory. In addition, there was evidence of step- Wise cognitive decline and focal neurological signs (eg., visual field cut) that correspond to the two frank cerebrovascular accidents. This corresponds to his high score on Rosen's modifi- cation of the HIS that is well within the range suggestive of vascular dementia. Third, there is evidence of functional decline, which is a neces- sary component of any dementia diagnosis, Finally, these deficits cannot be explained by psychiatric factors or another degenerative con- dition. Specifically, dementia of the Alzheimer’s type (DAT) can be ruled out given the patient's relatively young age and the absence of signifi- cant memory deficits, including rapid forgetting, a hallmark feature of DAT. ‘This case is a prototypical example of multi- infarct dementia. However, there are a few aspects of this case that are not necessarily tequired fora diagnosis of other vascular demen- tia subtypes, specially subcortical vascular dementia. Although a stepwise decline and a fluctuating course are often considered a key feature of the clinical course in vascular demen- tia, this is only the case if there are frank cere- brovascular accidents with obvious functional impairment, such as hemiparesis or sudden onset of aphasia. Often, the patient presents with insidiouis cognitive and functional decline that corresponds with silent strokes or progression of microvascular ischemic disease. In addition, the patient’ chief cognitive complaint is often “memory problems” which can lead other Providers to suspect early Alzheimer's disease. RST rename Nn emi caimtsioRe Ghee Hons enttaeesseanOnAt ; i I Vascular Dementia However, on neuropsychological testing, these “memory problems” are often related to execu- tive dysfunction and problems with retrieval. 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