Frontotemporal Dementia, Lewy Body Disease and Other Dementias

What is frontotemporal dementia?

Spectrum of clinical syndromes involving degeneration of the frontal and temporal lobes.

How is FTD different from other dementias?

Usually has a younger age of onset (45-65 years old)

Significant atrophy in frontal and temporal lobes

Significant behavioral and language deterioration.

Basically you either forget how to speak or start acting really odd.

What are the risk factors for FTD?

Head trauma, thyroid disease.

What is the pathophysiology of FTD?

Tau protein deposition

Astrocytosis (inflammatory, nutritional cells working over time)

Microvacuoles formation

What type of aphasia is seen in FTD?

Primary progressive aphasia

What are the clinical presentations of FTD?

Behavioral disturbances

Disinhibition

Impulsivity

Witzelsucht (pointless sense of humor)

Impersistence

Loss of social awareness

Neglect of personal hygiene

How is FTD diagnosed?

Post-mortem examination.

Clinical presentation and history

Neuroimaging showing frontal lobe and temporal lobe atrophy more pronounced

What is the treatment of FTD?

No cure. Treat symptoms, especially behavioral.

Mood stabilizers

Supportive care.

What are the subtypes of Lewy Body dementia?

Dementia with Lewy Bodies and Parkinson's Disease Dementia

What is the pathophysiology of all Lewy Body disease?

Aggregation of alpha synuclein in the brain, primarily in basal ganglia = Lewy Bodies.

What differentiates dementia with Lewy Bodies from PD dementia?

In PD dementia, Parkinson's signs appear first and dementia develops later (at least a year later)

In dementia with Lewy body, dementia comes first and then Parkinsonism develops (at least a year later)

What is the clinical manifestation of dementia with Lewy Bodies?

Waxing and waning cognitive dysfunction, deficits in attention and alertness.

Visual hallucinations with extra-pyramidal symptoms (happens 1 year after cognitive decline)

How is Lewy Body dementia different from Alzheimer's dementia?

More visuospatial abnormalities

Impaired concentration and attention

Apathy and loss of initiation

Daytime hallucinations (common in early disease)

Parasomnias (being chased, thrashing about, yelling during sleep)

How is Dementia with Lewy Bodies diagnosed?

Post-mortem exam

Clinical diagnosis based on history

MRI of brain, labs to rule out other causes.

How do you treat Dementia with Lewy Bodies?

Cholinesterase inhibitors (Donepezil) are first line.

Symptomatic treatment

Extrapyramidal symptoms treated with Carbidopa-Levodopa.

How do you diagnose Parkinson's Dementia?

Cognitive impairment occurs at least 1 year AFTER diagnosis of Parkinson's disease.

What medication is the only FDA approved medication for hallucinations in PD and PDD?

Primavanserin. Also used off label to treat hallucinations in Lewy Body dementia.

What is vascular dementia?

2nd most common type of dementia.

Decline in function due to a cerebrovascular event (stroke). Can be large vessel, small vessel, microvascular disease affecting periventricular white matter.

What is the clinical presentation of vascular dementia?

Abrupt onset of symptoms. Symptoms will vary based on size, location, and number of cerebral insults.

What are the risk factors of vascular dementia?

Correlates to cardiovascular disease:

HTN

DM

Smoking

Dyslipidemia, advanced age, obesity, sleep apnea.

How do you diagnose vascular dementia?

Radiographic evidence of cerebrovascular accident is key, this MUST be associated with the onset of cognitive changes, NOT a remote/old infarct.

What is the treatment for vascular dementia?

Manage vascular risk factors: aspirin, statins, BP regulation

Treats the symptoms present with cognitive and physical rehab

Lifestyle modifications.

How is memory loss affected in vascular dementia?

It is often less prominent than in AD, as the symptoms depend on what part of the brain is affected in the stroke (most strokes occur in the ACA and MCA)

Describe HIV-related dementia

Not commonly seen anymore, as the disease is more easily managed now than before.

Patient must have diagnosis of HIV for several years.

What is the pathophysiology of HIV-related dementia?

Neurotoxic HIV proteins and upregulation of immune and inflammatory mediators cause damage to CNS.

What is the clinical manifestation of HIV-related dementia?

Triad of cognitive impairment, motor impairment and behavioral changes.

Memory is spared until later in the disease course.

Visuospatial reasoning and language largely spared.

How is HIV-related dementia diagnosed?

Clinical diagnosis of HIV and low CD4 count. Brain MRi show increased signal in the subcortical white matter and central atrophy.

How do you treat HIV-related dementia?

Low HIV RNA in plasma and CSF. As long as you treat the HIV, you will get better!

What is the special consideration for those with T21?

They have an increased risk of developing AD and at an earlier age! Standardized cognitive assessments are NOT reliable. Do labs to rule out other things, see if they've had a change in environment or meds that could be causing symptoms, and do neuro-imaging if appropriate.