Vascular Dementia

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<ul><li> 1. Vascular Dementia</li></ul> <p> 2. Disclosures AGA Medical Orasi Medical NINDS National Institute on Aging Alzheimers Association 3. Post-stroke Neuropsychiatric Problems Depression Anxiety Apathy Pathologic laughing and crying Aggression Psychosis Mania Obsessive-compulsive disorder Cognitive problems 4. DementiaWorking definition: An acquired and persistent impairment in intellectual function with problems in at least three of these areas: Memory Language Visuospatial skills Emotions and personality Complex cognition 5. Dementia The impairment is sufficient to interfere with usual social and occupational activities Dementia is not always progressive or irreversible 6. Stroke and Dementia Terminology Multi-infarct dementia Vascular dementia Vascular cognitive impairment Vascular mild cognitive impairment 7. Dementia Frequency 66-70 % Alzheimers 10-25% vascular dementia (#2 for today) Largest group may be mixed BrainNet Europe Consortium 53% of 3,300 autopsied brains Similar numbers from smaller series in US Up to 40% Alzheimers / vascular Depends on the criteriaQiu2007,Schneider2007,Kovacs2008 8. Vascular Dementia Location Multiple locations A key location producing deficits in multiple areas of cognition Diffuse pathology: typically slows more than disconnects Size: 50-100cc of brain or more associated with dementia 9. Classification Multi-infarct dementia Strategic infarct dementia Subcortical ischemic dementia Hypoperfusion dementia Mixed (usually with Alzheimers)***************************** Hemorrhagic dementia Dementia due to specific arteriopathies Vascular mild cognitive impairment 10. Multi-infarct dementia Cumulative cognitive deficits from multiple strokes Depends on: Number of strokes Location ? total volume of infarcted brain (50-100cc +) Most commonly recognized 11. Strategic infarct dementia Angular gyrus Genu of the internal capsule Thalamus Caudate Cerebellum 12. Angular gyrus infarct Dominant hemisphere Gerstmanns (L-R disorientation, fingeragnosia, acalculia, agraphia) Fluent aphasia Non-dominant hemisphere Visuospatial disturbance Attentional disturbance/neglect 13. Internal capsule - genu infarct Acute confusional state Chronic attentional deficits Apathy Psychomotor slowing Verbal memory deficits 14. Thalamic infarct Language Verbal memory Visuospatial processing Personality change Apathy May have bilateral thalamic injury Paramedian artery or venous Chui2007 15. Caudate stroke Abulia / apathy Agitation / hyperactivity Attentional deficits Language problems (left) Neglect (right) 16. Cerebellar infarct Working memory Verbal memory Visual-spatial function Executive function Schmahmann 1998, 2006 17. Subcortical ischemic dementia Often grouped together as subcortical or small vessel disease Includes both small infarcts (lacunae) and more diffuse white matter disease 18. Lacunar infarcts and cognition 16 patients with single symptomatic lacunar infarct -- deep white matter Scattered, excluding genu of internal capsule, 11 on L and 5 on R Not right, different, tired Normal on most neuropsych testingVanZandvoort1998 19. Lacunar infarct All had deficits in attention and the speed of mental processing Trouble with complex or multiple tasks, and time pressure Van Zandvoort 1998, J. Anderson 2008 20. White matter diseaseAKA Leukoaraiosis Senile leukoencephalopathy Progressive subcortical vascular encephalopathy Subcortical ischemic leukoencephalopathy Subcortical arteriosclerotic encephalopathy Lacunar dementia Binswangers disease (encephalitis subcorticalis chronica progressiva)Filley 2001, Schmahmann 2008 21. White matter diseaseCommon risk factors: Pathology includes: Age Demyelination Hypertension Axonal loss Diabetes Gliosis Atherosclerotic disease Assumed to beischemicFilley 2001, Schmahmann 2008 22. White matter disease Only modest correlation of white matter burden with cognitive performance Correlates better with transition from normal cognitive function to MCI, than from MCI to dementia White matter burden correlates with rate of decline in population studies 23. White matter diseaseMost affected: Motivation Processing speed Executive function Memory (retrieval rather than encoding) Common instruments like the MMSE may be less useful in this setting Association with depression Chui 2007 24. Disrupted periventricular cholinergic projection axons are presented by a dashed line. Modified from: Bohnen, N. I. et al. Neurology 2009;72:1411-1416 25. Global hypoperfusionAffecting: Memory Attention Language Motivation/apathy Praxis Visuospatial function 26. Evolution of dementia Demons and other evil spirits Not syphilis Hardening of the arteries Alzheimers disease Alzheimers + vascular and other mixed pathologies 27. Stroke and AlzheimersAlzheimers associated with: Diabetes High serum viscosity Hypertension High fibrinogen Atrial fibrillation Prior stroke/TIA Elevated cholesterol Excessive alcohol Elevated homocysteine Smoking Inflammation De La Torre 2002, Qui 2007 28. Alzheimers DiseaseBetter with:Increased Education: Reduced risk /delayed onset / modified course /testingeffect?Mentally stimulating activitiesSocial interactionsPhysical activity Qui 2007, Wilson 2009 29. Stroke/Alzheimers Genetics APOE 4/4 prior stroke/TIA gives 5x risk of developing Alzheimers Genes with potential link to Alzheimers include TNF alpha polymorphism with CT or TTgenotype) Angiotensin converting enzyme gene Lipoprotein lipase gene Beta-fibrinogen gene Nitric oxide synthase lll gene Low-density lipoprotein gene 30. Stroke and Alzheimers Alzheimers disease pathology includes: Capillary abnormalities BBB changes Arteriolar lipohyalinosis Amyloid angiopathy (98%) Wallerian degeneration Vascular changes were described by Alzheimer Schmahmann 2008 31. Stroke and Alzheimers Overlap clinically, genetically, and pathophysiologically The more we know the greater the overlap Insight into the complexity and variability of both Alzheimers and vascular injury 32. Vascular risk factors Hypertension: reduced risk of dementia with treatment with antihypertensives ~ longer than 5 years under age 75 compared with untreated hypertensive subjects and normotensive controlsHoffman Neurology 2009 Weak to no evidence for statins, reducing BP (without prior cerebrovascular disease), nonsteroidals, B12, specifically for cognitive declineBowler 2007, Cochrane 2006, 2009 33. General Treatment of Dementia Counseling and education Planning: job, living situation, $$$, caregivers Attention to driving Attention to driving Attention to driving Avoid drugs that worsen mental status (benzodiazepines, anticholinergic drugs) 34. Behavioral Problems Glasses/hearing aids Lights Reorientation Protect sleep Control stimulation Pictures/familiar objects from home Calendars/schedules Memory books 35. Behavioral ProblemsCaregiver response:Identify the problemReassuranceRedirection/distractionCalm approach 36. Stay CalmIf you can stay calm while everyonearound you panics, you should stop andwonder if you really understand thesituationAnonymous 37. Symptomatic Treatment Depression SSRIs, trazodone, nefazodone, ECT, TMS Psychosis Newer antipsychotics: olanzapine, risperidone Smallest dose, limited time Little evidence of benefit in trials Anxiety SSRIs, buspirone 38. Symptomatic TreatmentAgitation/aggressionEnvironmentTreat medical illnessAtypical antipsychoticsValproic acid, carbamazepine, beta-blockersBuspironeTrazodone 39. Behavioral issues Importance of exercise Staying mentally active Staying active socially 40. Cognitive Treatment Dopamine agonists Stimulants Acetylcholinesterase inhibitors 41. Cognitive Treatment Acetylcholinesterase inhibitors for cognition and behavior limited evidence for donepezil, rivastigmine, andgalantamine cautious interpretation given mixed dementias instudy off-label use (for the moment) Memantine -- NMDA antagonist modest and conflicting evidence may havecognitive benefit in mild to moderate VaD CDP-choline -- limited benefit over short-term The benefits are subtleCochrane Database of Systematic Reviews 2005-9 42. Summary Review of some of the cognitive effects of vascular disease Appreciation of the interaction of vascular disease and Alzheimers Limited options for treatment Emphasizes the need for risk factor modification and prevention 43. Evaluation of the patient 44. Folstein MMSE Questions (Total of 30 points) Orientation (10 points) Patient identifies time and place Registration (3 points) and Recall (3 points) Patient recalls objects at 1 and 5 minutes Attention and Calculation (5 points) Patient spells a word backwards or serial 7s Language (8 points) Tests processing language Visual-spatial: pentagons (1 point) 45. MMSE: Educational and Age Norms Fourth Grade Education Ages 18 to 69: Median MMSE Score 22-25 Ages 70 to 79: Median MMSE Score 21-22 Age over 79: Median MMSE Score 19-20 Eighth Grade Education Ages 18 to 69: Median MMSE Score 26-27 Ages 70 to 79: Median MMSE Score 25 Age over 79: Median MMSE Score 23-25 High School Education Ages 18 to 69: Median MMSE Score 28-29 Ages 70 to 79: Median MMSE Score 27 Age over 79: Median MMSE Score 25-26 College Education Ages 18 to 69: Median MMSE Score 29 Ages 70 to 79: Median MMSE Score 28 Age over 79: Median MMSE Score 27Crum1993 46. 47. 48. Frontal Assessment Battery Standardized test Age standardized norms available 18 points 49. FrontalAssessmentBaCery 50. 51. Approach to the patientDiagnostic studies Electrolytes, renal function, liver function, CBC, TSH, B12 MRI or CT scan in most patients 52. Selected patients Lumbar puncture May eventually have useful CSF profiles of tau, phospho-tau, amyloid-beta, metalloproteinase 9,lightneurofilament subunit of myelin Toxicology RPR, HIV Genetic testing EEG Neuropsychological testing Functional imaging Stroke evaluationBibl2007,2008 53. Hachinski Ischaemia Score Abrupt onset 2 History of hypertension 1 Stepwise deterioration 1 History of strokes 2 Fluctuating course 2 Evidence of associated Nocturnal confusion 1 atherosclerosis 1 Relative preservation of Focal neurological personality 1 symptoms 2 Depression 1 Focal neurological signs 2 Somatic complaints 1 Emotional incontinence 1 HachinskiVC,CerebralbloodowindemenAa. ArchNeurol.1975;32:6327. 54. NINDS - AIREN criteria for the diagnosis ofvascular dementia1. Dementiadefined by cognitive decline from apreviously higher level of functioning andmanifested by impairment of memory and of twoor more cognitive domains (orientation,attention, language, visuospatial functions,executive functions, motor control, and praxis),preferable established by clinical examinationand documented by neuropsychological testing;deficits should be severe enough to interfere withactivities of daily living not due to physical effectsof stroke alone. 55. Exclusion criteria: cases with disturbanceof consciousness, delirium, psychosis,severe aphasia, or major sensorimotorimpairment precludingneuropsychological testing. Also excludedare systemic disorders or other braindiseases (such as AD) that in and ofthemselves could account for deficits inmemory and cognition. 56. 2. Cerebrovascular disease, defined by the presence offocal signs on neurologic examination, such ashemiparesis, lower facial weakness, Babinski sign,sensory deficit, hemianopia, and dysarthria consistentwith stroke (with or without history of stroke), andevidence of relevant CVD by brain imaging (CT orMRI) including multiple large vessel infarcts or a singlestrategically placed infarct (angular gyrus, thalamus,basal forebrain, or PCA or ACA territories), as well asmultiple basal ganglia and white matter lacunes, orextensive periventricular white matter lesions, orcombinations thereof. 57. 3. A relationship between the above twodisorders, manifested or inferred by thepresence of one or more of the following:(a) onset of dementia within 3 monthsfollowing a recognized stroke; (b) abruptdeterioration in cognitive functions; orfluctuating, stepwise progression ofcognitive deficits. 58. II. Clinical features consistent with the diagnosis ofprobable vascular dementia include the following:(a) Early presence of gait disturbance (small-step gaitor marche a petits pas, or magnetic, apraxic-ataxic orparkinsonian gait); (b) history of unsteadiness andfrequent, unprovoked falls; (c) early urinaryfrequency, urgency, and other urinary symptoms notexplained by urologic disease; (d) pseudobulbarpalsy; and (e) personality and mood changes, abulia,depression, emotional incontinence, or othersubcortical deficits including psychomotorretardation and abnormal executive function. 59. III. Features that make the diagnosis of vasculardementia uncertain or unlikely include (a) earlyonset of of memory deficit and progressiveworsening of memory deficit and progressiveworsening of memory and other cognitivefunctions such as language (transcortical sensoryaphasia), motor skills (apraxia), and perception(agnosia), in the absence of corresponding focallesions on brain imaging; (b) absence of focalneurological signs, other than cognitivedisturbance; and (c) absence of cerebrovascularlesions on brain CT or MRI. 60. IV. Clinical diagnosis of possible vasculardementia may be made in the presence ofdementia (section I-1) with focal neurologicsigns in patients in whom brain imagingstudies to confirm definite CVD are missing;or in the absence of clear temporalrelationship between dementia and stroke;or in patients with subtle onset and variablecourse (plateau or improvement) ofcognitive deficits and evidence of relevantCVD. 61. V. Criteria for diagnosis of definite vasculardementia are (a) clinical criteria forprobable vascular dementia; (b)histopathologic evidence of CVD obtainedfrom biopsy or autopsy; (c) absence ofneurofibrillary tangles and neuritic plaquesexceeding those expected for age; and (d)absence of other clinical or pathologicaldisorder capable of producing dementia. 62. VI. Classification of vascular dementia for researchpurposes may be made on the basis of clinical,radiologic, and neuropathologic features, forsubcategories or defined conditions such as corticalvascular dementia, subcortical vascular dementia,BD, and thalamic dementia.The term "AD with CVD" should be reserved toclassify patients fulfilling the clinical criteria forpossible AD and who also present clinical or brainimaging evidence of relevant CVD. Traditionally,these patients have been included with VaD inepidemiologic studies. The term "mixed dementia,"used hitherto, should be avoided. 63. Reference Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993 Feb;43(2):250-60.</p>


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