DEMENTIA

1. DEMENTIA Michael J. Mintzer, MD Associate Professor of Medicine University of Miami School of Medicine Director of Community Academic Partnerships Miami VAMC and GRECC

2. Dementia Learning Objectives: • Define dementia • Describe the common dementias in the elderly • Differentiate the issues of reversibility, comorbidity, and arrestability • Describe the current dilemmas in the pharmacological treatment of dementia

3. Dementia Definition A: The development of multiple cognitive deficits manifested by both: (1) Memory impairment (impaired ability to learn new information or to recall previously learned information) (2) One or more cognitive disturbances: (a) aphasia (language disturbance) (b) apraxia (impaired ability to carry out motor activities despite intact motor function) (c) agnosia (failure to identify objects despite intact sensory function) (d) disturbance in executive functioning (planning, organizing, sequencing, abstracting, etc.)

4. Dementia Definition B: The cognitive deficits in Criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from previous level of functioning C: Features specific to the clinical presentation of (1) Alzheimer's Disease, or (2) vascular disease, or (3) other general medical condition, or (4) the persisting effects of a substance, or (5) multiple etiologies or (6) "not otherwise specified.“ D,E,F: The cognitive deficits in Criteria A1 and A2 are not due to a different specific illness (i.e., a different form of dementia, delirium or psychiatric illness).

5. Dementia Etiologies • Degenerative (Alzheimer’s, Lewy body, Parkinson’s) • Vascular (MID, large stroke, vasculitis, Binswanger’s) • Metabolic (hypothyroid, B12 deficiency) • Infectious (AIDS, Syphilis, late post TB) • Hypoxic (s/p CPR, s/p anesthesia?, s/p RT?) • Toxic (heavy metal) • Intracranial lesion (mass) • Trauma (dementia pugilistica)

6. Dementia Most Common Causes of Dementia in the Elderly • Alzheimer’s disease (AD)(50-60%)* • Diffuse Lewy body disease (DLBD)(15-20%) • Vascular dementia (VD)(15-20%) • Parkinson’s dementia (1-3%) • Frontotemporal dementia (1-2%) • All other *In the past, DLBD was included in this category. In addition, up to 10% of dementias are mixed AD plus VD

7. Dementia Reversible or not! • The definition does NOT define permanence of the lesion (pseudodementia?) • Data suggests there are very few reversible dementias in the elderly (depression, chronic intoxication by medication, hypothyroidism) (Larson) • Co-morbid conditions account for most of the reversibility in dementia in the elderly (Larson) • “Arrestable” or “Remediable” may be better terms (Maletta)

8. Dementia Minimum Cognitive Impairment (MCI) • Definition • What do we do with it?

9. Dementia Clinically helpful EARLY clues • Alzheimer’s Memory • Diffuse LBD Attention, Exec Func, Visio-spatial • Vascular Focal signs, temporal relationship • FT / Pick’s Behavioral, social skills, hygiene • Parkinson’s Dementia does NOT occur early in Parkinson’s disease

10. Dementia Alzheimer’s disease • Deposition of beta-amyloid in senile plaques diffusely in the brain, often around blood vessels • Neurofibrillary tangles • Loss of neurons • Brain shrinkage especially cortex

11. Alzheimer’s Risk Factors • Age • Prevalence doubles every 5 years after age 60 • Family History • Fourfold increase risk overall. The presence of the ApoE4 allele increases risk but is not predictive. • Gender • Woman probably more than men • Head Trauma • Repeated, especially in men • Down’s Syndrome • Characteristic brain pathology by age 40 • Educational Level / Mental Activity

12. Risk Factors (continued) • Estrogen plus progesterone • Doubles risk of dementia • Environment ? • Hypertension ? • Elevated Cholesterol ? • Depression ?

13. Dementia Medications for Alzheimer’s disease • Acetylcholinesterase inhibitors: indicated for mild to moderate dementia. Increases acetylcholine in synapses • Memantine (Namenda): indicated for moderate to severe dementia and used with ACI. Selective blocks the excitotoxic effects of glutamate while allowing the physiologic transmission for normal cell function

14. Acetylcholinesterase inhibitors Do they work when they work? • Using family – fewer problem behaviors • Using NH placement – save ~2 yrs • Using metrics (MMSE) - minimal incremental improvement

15. Memantine • Works for moderate to severe • Works alone • Works with ACI

16. Alzheimer’s Disease What else works? • Vitamin E • Statins?

17. Factors Contributing to [Aßs] [Aßs] 24S-OH cholesterol cerebrocholesterol cholesterol ApoE4 Aging inflammation LRP APP CNS growth/repair Adapted from Hazzard 2004 AGS annual meeting

18. Cholesterol & Alzheimer’s • In human studies there are more ß-amyloid plaques in patients dying from heart disease than from other causes (Sparks 1991) • Cholesterol >240 between age 40-50 predicted higher AD risk 30 years later (Notkolo 1998) • In animal studies, rabbits fed high cholesterol diet led to plaques that regressed when cholesterol was removed What do we do with our effective cholesterol lowering drugs? Adapted from Hazzard 2004 AGS annual meeting

19. Cholesterol & Alzheimer’s • It’s too early to recommend adding “statins” for the treatment of Alzheimer’s • We need well controlled studies across the spectrum of dementia Adapted from Hazzard 2004 AGS annual meeting

20. Let’s Add to the Confusion • ACI and memantine(?) might work for vascular dementia, too ! ! !

21. Summary • Dementia is easy to diagnose • There are features that help differentiate the common dementias in the elderly • Reversible dementias are uncommon in the elderly but many dementias are arrestable • Treating comorbid conditions allows those with dementia to function at their best • Current drugs used for Alzheimer’s may help vascular dementia as well • Vitamin E is worth a try but not statins