1 What if it s not Alzheimer s? Update on Lewy body dementia and frontotemporal dementia
2 Dementia: broad term for any acquired brain condition impairing mental function such that ADLs are impaired. Includes: Alzheimer s disease Multi-infarct dementia (due to strokes) Lewy body dementia Frontotemporal dementia many others
3 Outline for tonight Lewy body dementia Frontotemporal dementia Treatment Research Support programs
4 Outline for tonight Lewy body dementia PDD (Parkinson s Disease Dementia) LBD (Lewy body dementia) Frontotemporal dementia Behavioral variants Language variants Genetic variants Treatment Research Support programs
5 Some definitions : Dementia = any acquired brain condition that interferes with the ability to think and to carry out routine daily functions
6 Some definitions : Dementia = any acquired brain condition that interferes with the ability to think and to carry out routine daily functions Alzheimer s disease = the most common cause of dementia, characterized by plaques and tangles in brain
7 Some definitions : Dementia = any acquired brain condition that interferes with the ability to think and to carry out routine daily functions Alzheimer s disease = the most common cause of dementia, characterized by plaques and tangles in brain
8 Some definitions : Dementia = any acquired brain condition that interferes with the ability to think and to carry out routine daily functions Alzheimer s disease = the most common cause of dementia, characterized by plaques and tangles in brain Parkinson s disease = A disease of movement With dementia occurring Years after diagnosis
9 Some definitions : Dementia = any acquired brain condition that interferes with the ability to think and to carry out routine daily functions Alzheimer s disease = the most common cause of dementia, characterized by plaques and tangles in brain Parkinson s disease = A disease of movement with dementia occurring years after diagnosis
11 Cognitive Function in PD a motor disease without a significant cognitive component: Classical View: by the absence of any injury to the senses and to the intellect, (we conclude) that the morbid state does not involve the encephalon. ---James Parkinson, An Essay on the Shaking Palsy (1817)
12 Revised View: Cognitive impairment is a common feature of PD Cognitive impairment is a significant source of distress and disability
13 Dementia Prevalence of Cognitive Impairment in PD 20% of PD have mild cognitive impairment (MCI) at time of PD diagnosis 30-40% of all PD have dementia Up to 80% by 15 years into disease 4-6x greater than elderly without PD
14 What domains of mental function are affected in Parkinson s? Attention* Memory Executive function* Visuospatial function* Language function
15 Alzheimer s vs Parkinson s: Alzheimer s PD Dementia Attention Memory Executive Visuospatial Language
16 What causes cognitive decline in Parkinson s? Many causes Changes in neurotransmitters are part of the problem---but it s not the same neurotransmitters that cause the movement disorder
17 Motor Symptoms are Dopamine Responsive
18 Motor Symptoms are Dopamine Responsive
19 Motor Symptoms are Dopamine Responsive
20 Motor Symptoms are Dopamine Responsive
21 Cognitive symptoms are due to impairment in a different neurotransmitter: acetylcholine: Bohnen, Arch Neurol, 60:1745-8, 2003.
22 Bohnen, Arch Neurol, 60:1745-8, 2003.
23 Bohnen, Arch Neurol, 60:1745-8, 2003.
24 Bohnen, Arch Neurol, 60:1745-8, 2003.
25 Drugs to boost acetylcholine help in PD dementia:
28 Conclusions: Parkinson s dementia is distinct from Alzheimer s Neurotransmitters involved in dementia are distinct from the ones involved in impaired movements.
29 What is Lewy body dementia? A dementia characterized by: Parkinsonism Hallucinations Sensitivity to anti-psychotic medications Fluctuations Brain autopsy shows lewy bodies in the brain
30 What is Lewy body dementia? The cognitive profile looks like parkinson s dementia Brain autopsy shows lewy bodies in the brain
31 How is Lewy body dementia different from Parkinson s disease? In Parkinson s disease, the dementia appears several years after diagnosis of movement problems. In Lewy body dementia, the movement problems and the dementia come on together.
32 How is Lewy body dementia different from Parkinson s disease? Tremor is less common Slowness and stiffness are more symmetric Motor symptoms are less responsive to medication in lewy body dementia than in parkinson s disease
33 How is Lewy body dementia different from Parkinson s disease? In Parkinson s disease, hallucinations are promoted by the drugs used to treat Parkinson s disease. In Lewy body dementia, hallucinations appear without being triggered by any drugs.
34 What is Lewy body dementia? Sensitivity to antipsychotic medications is part of Lewy body dementia. Patients can become frozen from low doses of these medications Fluctuations in level of consciousness are also common in Lewy body dementia.
35 How is Lewy body dementia treated? Need to be careful with Parkinson s medicines, because they will increase hallucinations. Need to be careful with medicine for hallucinations, because it worsens parkinsonian motor symptoms. Some patients do well with medicines that increase acetylcholine.
36 The ability to increase brain acetylcholine is limited: Because acetylcholine also works on the stomach and intestines Most of the drugs that boost acetylcholine in brain also boost it in GI tract and cause nausea, vomiting, loose stools, diarrhea If only there was a way to boost acetylcholine in the brain without affecting the gut.
38 Research on Lewy body dementia 28 studies currently recruiting world-wide 1 study recruiting in Oregon
42 What can we do about hallucinations in Parkinson s dementia and Lewy body dementia The medications usually used for hallucinations make parkinsonism worse. One exception is clozapine, but there are risks with that drug which require weekly blood tests to monitor. A new approach to hallucinations in this population is needed.
47 Conclusions: New strategies for increasing acetylcholine in the brain may permit more effective treatment of Lewy body dementia. A new strategy for treating hallucinations in the setting of Parkinson s disease may eventually be applied to Lewy body dementia
48 Future directions for Lewy body dementia: Aimed at underlying pathology: Lewy bodies, the chief component of which is alpha synuclein:
49 Spread of Lewy bodies to thinking centers of the brain:
50 Experimental therapies trageting synuclein include: small molecule (ie, a pill) Immunotherapy (ie, antibodies, delivered by injection) Gene therapy
51 Support for Lewy body dementia: Alzheimer s Association Lewy Body Dementia Association
52 Frontotemporal dementia: Behavioral variant Language variant
53 Behavioral variant: disinhibited: 52 year old man: Trouble learning new tasks at work Gradual onset of disinhibited statements there is no filter Over-spends, over-tips Eats impulsively: Stuffs mouth full without swallowing, episodes of choking Acts impulsively: eg, jumped in white water with dog while out hiking
54 Behavioral variant: disinhibited: 52 year old man: Mmse =29/30 EXIT-25 =14/50 Normal neuro exam Bilateral frontotemporal atrophy on MRI scan
55 MRI in FTD:
56 Language variant: Primary progressive aphasia (PPA) 53 year old woman referred for declining language function Worked as a traveling motel clerk until one year prior to evaluation. Telephone calls to husband and sister became flat about years prior to eval. Laid off from work one year prior to eval.
57 Language variant-ppa She was referred to a local neurologist, who found normal EEG, normal MRI, and thought neurodegenerative disease unlikely. Social security examiner thought she was depressed and recommended ECT. Psychiatrist thought her language was impaired, doubted depression as the primary diagnosis, and referred her to another neurologist Chief complaint was difficulty with expressive language
58 Mental status exam mmse = 21/30 Orientation = 6/10 Attention = 2/5 ( DLORY ) Repetition = 0/1 obvious trouble with word-finding during spontaneous speech, to the point where even simple sentences were rarely fluent
59 labs Neuro exam: normal Brain MRI normal
60 Brain autopsy Frontotemporal dementia confirmed in both instances Note: Younger than Alzheimer s patients Memory is relatively preserved Behavior or language are markedly impaired With time, impairment generalizes and function declines
61 Brain autopsy Some variants of frontotemporal dementia, defined by brain autopsy: Pick s disease FTDP-17 Progressive supranuclear palsy Corticobasal degeneration
62 Genetics: FTDP-17 (rare) Progranulin (rare) C9ORF72: fairly common in familial FTD, also seen in sporadic cases
63 Genetics: FTDP-17 (rare) Progranulin (rare) C9ORF72: fairly common in familial FTD, also seen in sporadic cases The genetics does not predict the particular symptoms
64 Treatment of FTD SSRI s are recommended by most experts Otherwise symptomatic treatment on a caseby-case basis
65 Research on FTD 45 studies worldwide none in Oregon 7 in California, none are treatments
66 Support for FTD Association for Frontotemporal Dementia Cure PSP Alzheimer s Association
67 conclusions Lewy body dementia and frontotemporal dementia are distinct from Alzheimer s disease Ongoing research is under way to develop disease-modifying treatments. In the meantime, treatment is tailored to symptoms. Support for caregivers is available through a number of non-profit groups.
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