Non-Alzheimer’s Dementia

1. Non-Alzheimer’s Dementia Bobby Huff PharmD Candidate 2012

2. Alzheimers • Accounts for roughly 70% of dementia • 80% in patients over 90 • ~45% in patients in their 70’s • Disease is progressive and irreversible • Diagnosis confirmed upon autopsy • The cortex shrivels up, damaging areas involved in thinking, planning and remembering • Shrinkage in the hippocampus, an area of the cortex that plays a key role in formation of new memories • Ventricles grow larger • Disease is associated with formation of plaques and tangles in the brain tissue http://drpinna.com/can-diet-prevent-alzheimers-dementia-21735

3. Non-Alzheimers • Many diseases, disorders and medical conditions share some common symptoms with Alzheimer’s • Managed in many different ways • Several types • Vascular dementia • DLB ( dementia with lewy bodies) • Parkinson’s dementia • Frontotemporal dementia • Huntington’s disease • Dementia can also be caused by infectious diseases, tumors, head injuries or even thyroid problems

4. Non-Alzheimer’s • Not only about memory • Aphasia (language) • Apraxia (in ability to performed asked tasks) • Personality changes • Impaired executive function (problem solving) • Loss of object knowledge (agnosia) • Psychosis • Movement disorders

5. Vascular • Accounts for roughly 18 percent of dementia • Stroke interferes with blood flow to the brain • Can manifest d/t • Multiple small strokes ( infarcts) • Caused by blood clots or ruptured small arteries • Large stroke (post-stroke dementia) http://www.thirdage.com/hc/c/what-is-vascular-dementia

6. Vascular vs. Alzheimers • Vascular dementia can appear to be alzheimer’s because it appears with several of the same characteristics • Memory problems • Confusion • Disorientation • Trouble following directions • How its different • Recalling day to day events is impaired • But for example recalling the face of people is not impaired • Alzheimer’s generally affects both

7. Vascular • Signs of Vascular Dementia (stroke) • Quick onset and abrupt presentation • Memory loss could lead to hallucinations, w/draw or even aggravated/agitated moods • Garbled speech, loss of coordination or weakness on one side of the body • Diagnosis • MRI or CT scan will confirm or rule out the evidence of a stroke • Treating the factors which can lead to stroke can help slow the progress of dementia • These being: HTN, Hyperlipidemia, Diabetes, Smoking

8. Vascular • Treatment • No medications are approved for vascular dementia • The use of medications such as those used for Alzheimer’s may provide some benefit • Donepezil, Aricept etc.. • In 2006 Donepezil was linked to 11 deaths in a clinical trial when used in patients who had vascular dementia. There were 11 deaths in the study group compared to 0 in the control. But other studies have showed benefit with Donepezil

9. Dementia with Lewy Bodies (DLB) • Occurs when protein deposits in the brain • These are called Lewy Bodies – impede cognitive fx. • Discovered by Fredrick Lewy ~1900 http://missinglink.ucsf.edu/lm/ids_104_neurodegenerative/Case2/Case2Micro.htm

10. DLB • Widely considered as the 2nd most common form of dementia • Accounting for close to 20% of cases • DLB vs Alzheimer’s • Both include • Confusion • Concentration • Memory impairment • Hallucinations • Both are progressive but in Alzheimer’s people have good and bad days yet in DLB people can change in as little as an hour and can appear very extreme

11. DLB • REM sleep behavior disorder • Could be an early sign of DLB • Movements, gesturing and speaking while asleep • DLB • Patients also have • Mobility issues similar to Parkinson’s • Slow, stiff, shaky movements • Difficulty balancing • Shuffling gait

12. DLB • Diagnosing • A medical workup can help identify some symptoms and narrow down the disease states • Like Alzheimer’s dementia absolute diagnosis can only be confirmed with an autopsy • Treatment • No approved medications • Medications used in Alzheimer’s and Parkinson’s disease may provide some benefit in patients who have DLB

13. Parkinson’s disease • One out of five persons with Parkinson's can develop dementia • Its due to Lewy Body formation in • Brain • Brain stem • Vs. Alzheimer’s • Parkinson’s is usually first diagnosed and then the dementia related problems occur • Usually doesn’t involve problems with language

14. Parkinson’s Dementia • Diagnosed • Medical history • Physical exam • Neurological exam • *these are used to rule out other causes • Treatment • There are no approved medications • Overall therapy is designed to not only manage the Parkinson’s disease itself but it is also designed to manage the dementia related problems

15. Frontotemporal dementia • Associated with more rare diseases associated with the temporal lobes of the brain • Front of the temporal lobes • Examples • Picks Disease • Deposits of the tau protein (pick bodies) • They can aggregate in certain lobes and lead to affects in personality, memory and even behavior http://www.google.com/imgres?q=frontotemporal+dementia

16. Frontotemporal dementia • Vs. Alzheimer’s • FTD is associated with: • Impaired judgement • Personality changes • Various changes in mood • Language barriers and problems • Decrease in hobbies/activities • FTD is also progressive like Alzheimer’s • Yet personality and behavioral symptoms occur earlier and disorientation occurs later • It is most usually observed in the reverse order in Alzheimer’s • Also semantic memory (associated with the meanings of words and objects) as well as episodic (time) memory are affected • semantic>episodic

17. FTD • Patients with Frontotemporal dementia may also exhibit inappropriate behavior • They have little regard as to how people feel or what they think of their actions • Diagnosed • Medical exam • Brain scan (may show atrophy of frontal or temporal lobes) http://www.google.com/imgres?q=frontotemporal+dementia

18. FTD • Treatment • No treatment • Manage the patients symptoms as best as we can in order to improve the quality of life. http://www.riversideonline.com/health_reference/Brain-Spine-Stroke/DS00874.cfm

19. Huntington's Disease • Caused by a genetic abnormality • Huntingtin (HTT gene) • Leads to the destruction of nerve cells in the bran and lowers the levels of neurtransmitters • Causes declines • Mental • Emotional • Behavioral • These patients are born with the defective gene • Yet do not experience symptoms until middle age • A parent has a 50 % chance to pass the defective gene on to a child

20. Genetics • Transcription is regulated by an interplay between histoneacetyltransferases and histonedeacetylases. Researchers have found that mutant huntingtin protein (Htt) inhibits histoneacetylation by blocking histoneacetylases or recruiting them into aggregates. The reduction in histoneacetylation leads to decreased transcription. http://www.nature.com/nature/journal/v413/n6857/fig_tab/413691a0_F1.html

21. Huntington's disease • Vs Alzheimer’s • Both have • Personality changes • Mood swings • Disorientation • Attention and judgment can be impaired early on when the disease presents • Memory occurs later • Also commonalities with Parkinson’s • Involuntary movements appear • Jerky, clumsy, irregular http://neuroskeptic.blogspot.com/2010/10/cannabinoids-in-huntingtons-disease.html

22. Huntington’s Disease • Patients may also begin fidgeting • Eventually the patient will lose the ability to walk, talk and swallow • Diagnosed • HD is diagnosed by a blood test to look for the specific gene defect • Treatment • Must manage the symptoms, there is no cure or medical treatment. Increase meds vs. quality of life • Because each Huntington's patient is unique, drug treatment must be individualized • Treatment Algorithms are out there

23. Dementia via infectious disease • Bacterial or viral infections can enter the brain • For example HIV/AIDS this can cause a person to have memory and concentration problems. • Person’s may also see a loss of motivation and decreased interest in things that were recently enjoyed • Creutzfeld-Jakob disease (Mad Cow) • Very rare (1 in 1,000,000) • Infection by transmission of a prion (infectious protein) • Infect and destroy the brain’s nerve cells • Memory and behavioral changes caused by the prion progress rapidly

24. Diagnosis of ID • Blood Tests • Medical history • Neurological exam • EEG (electroencephalogram) • Brain scan • Cerebral spinal fluid analysis (spinal tap) • Autopsy is a definitive diagnosis • Holes will be visible in the structure of the brain (mad cow) http://commons.wikimedia.org/wiki/File:Variant_Creutzfeldt-Jakob_disease_(vCJD),_H&E.jpg

25. Other causes of dementia • Brain tumor • Head injury • Thyroid disorder • Metabolic disorder • Endocrine disorder

26. SOURCES • Rosenblatt A, et al. A physician's guide to the management of Huntington's disease. Huntington's Disease Society of America. http://www.hdsa.org/images/content/1/1/11682.pdf. Accessed December 5, 2011. • Gillian P. Bates Huntington's disease: Exploiting expression,Nature 413, 691-694(18 October 2001)doi:10.1038/35099656. Accessed December 10, 2011. • Newman E. Michael New NIST SRM Helps Improve Diagnosis of Huntington's Disease From NISTTech Beat: December, 2011. Accessed December 10, 2011 • Spencer, Paula. Non-Alzheimer's Causes of Dementia; http://health.msn/health-topcs/alzheimes-disease/non-alzheimers-causes-of-dementia • Various Authors.http://www.mayoclinic.com/health ; Accessed December 2011 • CJD (Creutzfeldt-Jakob Disease, Classic. Centers for Disease Control and Prevention. 2008-02-26. Accessed December 10, 2011. • Redefining Non-Alzheimer's Dementias, http://www.mayoclinic.org/medicalprofs/non-alzheimers-dementias.html, Accessed December 14, 2011