Dementias other than Alzheimer’s Disease

Genie Pritchett, MD Geriatrician, Senior Care of Colorado

Vice President Medical Services, Colorado Access

Dementia

Reduced mental skills impacting daily living, manifested by changes in: •Memory •Behavior •Language •Understanding (executive functioning) •Emotions

Three stories:

• “The baby is inside” • Doctor goes to high school reunion • Mayor of small town

Where is the Pathology?

What Kind of Insult?

Slow Process

Quick Event

How to Make a Diagnosis

• Clinical observation

• Genetic Biomarkers

• Protein Biomarkers

• Neuroanatomy

Conundrum

• High degree of overlap in presenting symptoms

• Compelling reason to identify specific diagnosis

• < 10 % cases reversed

Types of Dementia

• Frontotemporal Dementia - FTD

• Vascular Dementia

• Dementia with Lewy bodies

• Other dementias: alcoholic, CJD, others

Frontotemporal Lobar Degeneration

FTD diagnostic features

• Second most common variant, age < 65 years old

• Mean age 60 years old

• Survival 2 – 8 years

• Genetic in 40% of familial cases

• Common protein pathology with other dementias (Corticobasal degeneration, PSP, ALS, MND) (TDP-43 protein, FUS inclusions)

Progressive Non-fluent Aphasia Slow, Effortful speech, Stuttering, Misuse of grammar, Verbs>Nouns, Eventual mutism

Semantic Dementia Fluent but empty speech, Over-learned phrases, Loss of object identity, naming impairment, Loss of empathy

Behavioral Variant Decline in social conduct, inappropriate remarks, risk taking,

impulsive, loss of insight, emotional blunting, poor personal hygiene, compulsive use of instruments, poor attention and control, commonly misdiagnosed as depression or mental illness

Biology of FTD

• Mutation of an arm of chromosome 17 causing disruption of gene progranulin–

• Aggregation of Tau, Ubiquitin proteins ultimately destroying neuron.

• PNFA - Tau pathology

• Semantic - Ubiquitin pathology

• Behavioral - both

What can we do? • No cure, treatment for symptoms • SSRI beneficial for disinhibition, depression, repetitive

behaviors • Antipsychotics for aggressive, impulsive behaviors • Caregiver needs, Support groups, Counseling • Focus on functional needs, Social stressors, Behavioral

management, Coordination of care, • FTD Association

Dementia with Lewy Bodies

Lewy Body

Spectrum of Lewy Body diseases

• Dementia with Lewy Bodies (DLB) and Parkinson’s Disease with Dementia (PDD)

• Similar genetic and environmental risk factors:

Pesticide exposure, High soil manganese, Synthetic heroin, Neuroleptics

• Both dopamine and choline deficits

• Aggregation of alpha-synuclein protein = lewy body

Symptoms

• Both cognitive and motor symptoms

• Executive, visual-spatial deficits, Hallucinations, Delusion, Agitation, Memory preserved early on.

• Dramatic fluctuations within the course of a day, Fatigue and agitation

• Falls common, Autonomic dysfunction (Hypotention, Incontinence), Dizziness,

• Brady-Kinesia, Rigidity, Postural Instability, REM sleep disorder

Useful Tests

• Frontal executive and visual-spatial deficits

– Clock Drawing Test

• Diagnostic test: SPECT (dopamine binding)

• CSF analysis for tau and amyloid (normal tau, low amyloid)

Vascular Dementia

Vascular Dementia • Multi-infarct or stroke related • Risk factors: HTN, Smoking, DM, CAD, AFIB • By the time the disease manifests, modifying risk factors

may be too late • Aneurysm, cerebral hypoxemia, genetic vascular disease

also vascular related • Lesions occur throughout brain - many manifestations

Vascular Dementia

• Cortical - primary damage in the cortex. Memory, language, thinking, and behavior

• Subcortical – Below the cortex, emotions, movement, memory

Common symptoms

• Memory impairment, language disorder, motor weakness, gait abnormality, pseudobulbar palsy (emotional lability)

• Most common: psychomotor slowing, attention deficits, executive dysfunction

• Stepwise deterioration

CADASIL • Cerebral Autosomal Dominant Arteriopathy with

Subcortical Infarcts and Leukoencephalopathy Small artery disease - newly described mean age 45

• Sx: migrane with aura, subcortical ischemic events, mood disorder, apathy

• NOTCH 3 gene on Chromosome 19 (AD) got gene, got disease

• Pathologic hallmark: granules in media of arterioles (seen on skin biopsy)

• Genetic testing: ethical issues

Rapidly Progresive Dementias

• Creutzfelt Jacob Disease - Mad Cow Disease

• Limbic and Hashimoto encephalopathy

• Infectious, autoimmune, paraneoplastic

Creutzfelt Jacob Disease - Mad Cow Disease

Creutzfeldt Jacob

• Prion protein 5-12 month course

• 50-70 y/o

• Gravest prognosis in neurology “The great mimicker” – Cortical – cognitive – Cerebellar – motor – Extrapyramidal – behavioral and movement

(tremor, myoclonus, dystonia) • Characteristic EEG, myoclonus, pulvinar sign on MRI

Limbic Encephalitis

• Inflammatory encephalitis caused by antibodies reacting against a tumor - most common is the anti-Hu associated with small cell lung cancer, can cause memory loss, panic attacks, cerebellar degeneration, vertical gaze palsy, limb rigidity, dystonia, narcolepsy, REM sleep disorder

Hashimoto’s encephalopathy

• Abnormal high levels of thyroid antibodies • Often have other autoimmune diseases

such as diabetes, lupus, Sjogren • Tremor, ataxia, hallucinations, stroke-like

episodes, confusion, mood and behavioral disorder

• MRI findings are non-specific, generalized atrophy, cortical and subcortical changes

Other Causes

• Infectious causes – syphilis, lyme disease, HIV associated dementia, Whipples

• Toxic/ metabolic – Vit B12, Thiamine, niacin, folate deficiencies, uremic encephalopathy, hepatic encephalopathy, heavy metals (bismuth, lithium, mercury, arsenic, lead)

• Autoimmune - paraneoplastic limbic encephalitis, hashimoto encephalopathy, lupus cerebritis, sarcoid

Wernicke-Korsakoff

• “Let granny have her drink” – Frontal lobe greatest impact: poor judgement,

difficulty with decisions, lack insight

• Also have memory and motor symptoms • TX - replace thiamine

Diabetes and Dementia

• Insulin induced hypoglycemia - rapid cognitive changes

• Chronic hyperglycemia - cerebral microvascular disease

• Type 2 DM has a 1.5-2.5 fold increase risk of dementia

• Central pontine myelinolysis (osmotic demyelination) – rapid correction of low sodium – “locked in syndrome”

Prevention • Causal disease prevention (stroke, blood

pressure, alcoholism, head injury, HIV/AIDS) • Early detection

Planning

• Caregiver support • End of Life Issues

Chocolate Anyone?????

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