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Home , Basal ganglia disease, Bradyphrenia, Vascular dementia

Vascular Cognitive Impairment and Frontal-Subcortical

Alice-Lee Vestner, MD Assistant Professor (Clinical) Alpert Medical School Providence VAMC Learning Objectives

• Subcortical refers to a clinical constellation of findings that result when there is damage to areas in the , basal gangia or stem nuclei with resulting impairment in frontal-subcortical circuits.

• The differential diagnosis for this clinical presentation is broad but can often be narrowed down by associated clinical findings

• The term “Vascular Cognitive Impairment” describes a spectrum of impairment ranging from VCI-ND to VCI- dementia to VCI-mixed and may present with a frontal- subcortical clinical picture.

History

• Early reports described a similar cognitive/emotional state – Huntington’s Disease (caudate) – Wilson’s Disease ( + ) – Lethargica() – Binswanger’s Disease

Turner, 2002 History

Progressive Supranuclear Palsy – Alpert et al, 1974: case series and literature review

Gait and Forgetfulness Slowness of thought eye movement disturbance Impairment in manipulating acquired knowledge Personality/mood changes

Huntington ’s Disease McHugh PR and Folstein, 1975 Lack of , agnosia,

Subcortical Dementia: an emerging concept

Cummings, 1984

Parkinson’s PSP Wilson’s HD Lacunar State BG Calcification

Pathologic changes involve: thalamus basal ganglia brain-stem nuclei

with sparing of the cortex 5 Subsequent debate re: usefulness of the term

“evidence to date suggests that intellectual dysfunction in DAT, HD, and PD may relate to a combination of cortical as well as subcortical degeneration.” Annals of , 1983

“ is a CLINICAL not an ANATOMICAL 1984 concept” Cummings, 2002 7 Cortical Dementia

Aphasia Apraxia Agnosia Amnesia(learning rather than retrieval deficit) Visuospatial fxn Frontal Cortex

8 http://www.indiana.edu/~p1013447/dictionary/assn_cor.htm Subcortical Dementia

Slowness of thought

Poor Retrieval of memories

Executive function deficits

Mood abnormalities/

Motor Disturbance Frontal Subcortical Circuits

Alexander, 1984 Frontal Subcortical Circuits: three behavioral

Apathy Executive Impulsivity akinetic mutism dysfunction Poor judgment emotional lability irritability Tekin and Cummings, 2002 sexual remarks Anterior cingulate in FTLD

Massimo, 2009 Anterior cingulate mediates motivated behavior Bilateral lesions can cause akinetic mutism /apathy loss of initiative Impersistence, slowness, bradyphrenia Loss of curiosity, tastes and preferences Often mistaken for depression May be normal on cognitive testing

12 Orbitofrontal Syndrome in FTLD

Personality Change Massimo, 2009 Behavioral disinhibition inappropriate jocularity impulsivity Emotional lability irritability explosive outbursts Poor judgement

Poor self care 13

Wolf, 2011 Dorsolateral Prefrontal Syndrome

• Loss of planning and internal goal-directed behavior • Loss of behavioral plasticity • Stimulus-boundedness; utilization behavior and other purposeless behaviors • Paucity of thought • Poor performance on specific cognitive testing Figure Legend: With Neurobehavioral Symptoms [A]: executive cognitive functioning (dark gray shading); [B]: personality (medium gray shading); [C]: motivation (light gray shading).

Marin, J Neuropsychiatry Clin Neurosci. 2012;24(4):384-393. Bonelli 2008 16 Bedside Testing of Executive Functioning

MMSE is not very helpful!! Supplement with Clock Drawing Trails Go-no go test: green don’t tap, red tap once Luria’s motor programs Luria’s recursive figures

Black, 2011

18 Diseases Presenting with the Frontal- Subcortical Dementia Syndrome

• Degenerative • Misc. – HD, PSP, PD, CBD, MSA – Normal Pressure • Vascular disorders – Dementia syndrome of Depression – Thalamic – Dementia Pugilistica – Subcortical Ischemic Vascular Disease – Alcoholic dementia • Metabolic disorders – Wilson’s Disease • Demyelinating – – AIDS dementia Complex

1960’s-70’s: AD was thought to be the primary < 1950’s Dementia was pathology commonly thought to be related to vascular causes “hardening of the arteries”

Now there is a greater appreciation for the intertwining of the two pathologies

20 Vascular Cognitive Impairment is a spectrum concept with deficits ranging from VCI-ND to mixed AD-VaD

MCI-Vascular origin

21 Moorhouse, 2008 Cerebral infarcts increase likelihood of dementia expression in patients with AD pathology

no strokes

Schneider, 2004 22 Risk Factors VaD

Demographic Age Male Lower educational level Shared risk Athlerosclerotic ? factors with AD HTN, Lipids, DM Cigarettes, MI Genetic CADASIL apo E4 Related Volume of tissue loss Bilateral Strategic disease 23 Gorelick, 2004 Clinical Forms of Vascular Cognitive Impairment

Acute ( poststroke)

Subacute (subcortical) MID Strategic

PCA Lacunar State Basal Forebrain Binswanger’s Thalamic CADASIL Inferior Genu CAA Caudate (Roman, 2005) Multi-Infarct Dementia MID

•Replaced older term cerebral arteriosclerosis

•VaD was thought to be the result of multiple small or large cerebral infarcts

•It was thought that a certain amount of brain tissue had to be destroyed (50-100ml)

•Now recognized as just one form of VaD

O’Brian, 2003 25 Strategic

Caudate nucleus Basal forebrain

• Thalamus

Globus Pallidus Angular gyrus

Black, 2005 Subcortical Ischemic Vascular Disease (SIVD)

Lacunar State Binswanger’s

Clinically homogenous subcortical syndrome Responsible for 36-67% of VD Insidious onset O’Brian, 2003 Roman et al, Lancet Neurology 2002 Diagnosis: DSM IV vs 5 Dementia (DSM IV)= Executive Cognitive decline Functioning

Language/Aphasia Involving multiple MEMORY spheres Sensory/Agnosia

Motor/ Apraxia

Functional Impairment

Functional impairment = MCI or Cognitive d/o NOS (VA) 29 Major Neurocognitive Disorder (DSM-5) Learning and Memory Cognitive decline Executive Involving one or Functioning multiple spheres Language/Aphasia

Functional Impairment Perceptual/ Motor Complex Attention Mild: deficits in instrumental ADL Social Cognition Moderate: deficits in basic ADL Severe: completely dependent

Functional impairment = Mild NCD 30 Perceptual/ Motor visual perception, visuo- constructional, perceptual-motor, Learning and praxis Memory Sustained attention, divided Complex Attention attention, selective attention, processing speed Language/Aphasia

Executive Behavior clearly out of Functioning acceptable social range; shows insensitivity to social standards of Social Cognition modesty in dress or of political, religious, or sexual topics of conversation. Makes decisions

without regard to safety. 31 Major or Mild Vascular Neurocognitive Disorder

A. Criteria are met for major or mild NC disorder B. The clinical features are c/w a vascular etiology – Either the onset of cog. deficits is temporally related to one or more vascular events or – Evidence for decline is prominent in complex attention and frontal-executive function C. There is evidence of CVD from history, physical or neuroimaging considered sufficient to account for deficits

32 Major or Mild Vascular Neurocognitive Disorder

• Probable Vascular NCD needs one of the following – Clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to CVD – The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events – Both clinical and genetic evidence of CVD is present (CADASIL)

33 Evaluation for vascular contribution to dementia

• History • Physical Exam (, balance, extensor plantar response, , exagerated DTR’s, palmar grasp) • Blood pressure measurement • Laboratory evaluation – Lipid panel/fasting glucose • MRI • Cognitive Evaluation – Tests of executive functioning/ attention

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Suggestive Motor Sx.

• Mild UMN signs (drift, reflex asymmetry, incoordination) • Gait disorder (slower, small steps) • Imbalance and falls • Urinary frequency and incontinence • • • EPS

Treatment of VaD

• Primary prevention – Minimize cerebrovascular and heart disease – Modify risk factors • Secondary Prevention – Stroke management • Disease management – Cognitive – Behavioral – Caregiver Support Risk Factor Modification

• Risk Factors: – CAD, CHF, afib – HTN, orthostatic hypotension – CVA, TIA – DM, OSA, smoking – (not modifiable)

Psychopharmacological Intervention

• Cholinesterase Inhibitors – Boost acetylcholine and can have a variable effect on cognition – May have a similar effect in VaD compared with AD but evidence is not as strong – Side effects: bradycardia, nausea, GI, abnormal dreams

38 Cholinergic hypothesis of VaD

• Penetrating arteries most affected by HTN • Deep nuclei, nucleus basalis of Meynert

http://www.radnet.ucla.edu

Roman, 2006 Cholinergic hypothesis of VaD

Selden, 1998; Schwartz 2003 IIa= B>>R “it is reasonable”

IIb= B≥R “may be considered”

Gorelick, 2011 Stroke 41 References

• Mackowiak-Cordoliani M, Bonbois S, Memin A, et al. Poststroke Dementia in the Elderly. Drugs Aging 2005: 22(6): 483-493 • O’Brian J, Erkinjuntti T, Reisburg B, et al. Vascular Cognitive Impairment. Lancet Neurology 2003; 2;89-98 • Erkinjuntti T. Subcortical ischemic vascular disease and dementia. Int Psychogeriatr. 2003;15 Suppl 1:23-6. • Black SE. Stroke risk and sequelae define therapeutic approaches. Postgraduate Medicine 2005;117;1. • Van Der Werf Y, Witter MP, Uylings HB, Jolles J. Neuropsychology of in the thalamus: A Review. Neuropsychologia 2000;38:613-627 • Roman GC., Erkinjuntti, Wallin A. Subcortical Ischaemic Vascular Dementia. Lancet Neurology 2002;1:426-436 References

• Fein G, DiSclafani V, Tanabe J et al. Hippocampal and cortical atrophy predict dementia in subcotical ischemic vascular disease. Neurology 2000;55:1626-35 • Okeda R, Murayama S, Sawabe M. Pathology of the Cerebral Artery in Bingswanger’s Disease in the Aged. Neuropathology 2004; 24; 21-29. • DeGroot JC, de Leeuw FE, Oudkerk m, et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 2000;47:145-151 • Stewart, John T. Diagnosis and Management of Frontal/Subcortical dementia. Presentation given at the AAGP, Orlando FL, 2008. • Garelick et al. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the american heart association/american stroke associations. Stroke:2011;42:2672-2713 References

• Merino JG, Hachinski V. Diagnosis of Vascular Dementia: Conceptual Challenges. In Current Clinical Neurology, Vascular Dementia: Cerebrovascular Mechanisms and Clinical Management. Ed: Paul RH, Cohen R. Ott BR, Humana Press Inc., Totowa NJ. 2005 • Kalaria RN, Kenny RA, Ballard CG, et al, Towards defining the neuropathological substrates of vascular dementia. Journal of the Neurological Sciences 226 (2004) 75– 80 • Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol 1975;32:632-637 • 1.)http://cclcm.ccf.org/vm/VM_cases/neuro_cases_CNS_vascular_pathology.ht m 2.)http://www-medlib.med.utah.edu/WebPath/CNSHTML/CNS039.html • 3) Abe K, JNNP, 1998; 65 • 4) http://www.med.harvard.edu/AANLIB/cases/case3/mr1/022.html • 5+6). http://braincampus.learnpsychology.com References

• Massimo L., Neuroanatomy of apathy and disinhibition in Frontotemporal Lobar Degeneration. Dement Geriatr Cogn Disord 2009;27:96–104 • Cummings, J. and Tekin, s. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: An Update. Journal of Psychosomatic Research 53 (2002) 647– 654 • Cummings JL, Benson DF. Subcortical dementia. Review of an emerging concept. Arch Neurol. 1984 Aug;41(8):874-9. • Alexander, G et al. Parallel organization of functionally segregated circuits linking Basal Ganglia and Cortex. Ann. Rev. Neurosci. 1986. 9: 357-81 • Moorhouse, P. Vascular cognitive impairment: current concepts and clinical developments. Lancet Neurology 2008; 7: 246–55 • Black, SE. Vascular Cognitive Impairment: Epidemiology, subtypes, diagnosis and management. J R Coll Physicians Edinb 2011; 41:49–56

45 References

• Bonelli R. and Cummings, J. Frontal- Subcortical Dementias. The Neurologist 2008;14: 100–107

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