Patient Cases IM approach to Dementia Wendy Kohatsu, MD Sept 2012 82 yomale wife brings him in b/c he forgets things, loses his keys, gets lost in supermarket, and then tends to lose his temper easily. 59 yowoman h/o cognitive decline, MRI 2009 c/w significant atrophy. Rx: CoQ10, alpha lipoicacid, 1 gmomega-3, DHEA 100 mg, gingko, ginseng, Brain Fitness program, gardening; just got P.A.P. for donepezil (Aricept). Dementia Definition: Major impairment in learning and memory plus one of following: Impairment in handling complex tasks Impairment in reasoning Impairment in spatial ability and orientation Language impairment Severe enough to interfere with daily function (work, social, or relationships) NOT accounted for by other psychiatric or systemic disorder. Types of Dementia Alzheimer s disease (AD) - 60-80% Vascular dementias (multiinfarct) 10-20% Other: Parkinsons 5% Alcohol-related Frontotemporal(Pick s Disease) Lewy-body (see rapid decline, hallucinations, motor def) Other neurodegenerations (e.g. Huntingtons) Neuroepidemiology 2007; 29:125 Clinical Evaluation- History Obtain a clear description of problem behavior, temporal onset, course, circumstances Assess ability to express basic needs (hunger, thirst, fatigue) R/o delirium acute/rapid change (dehydration, UTI, pneumonia, angina, constipation, pain, uncontrolled diabetes mellitus) 8 years average. Range 2-20 years 1
Clinical Evaluation- History Look for mood disturbance(sadness, irritability, withdraw) Check medications always suspect the meds Pain meds, anti-cholinergics, any psych meds, antihistamines Remember to ask about alcohol usein elderly. Ask about environmental precipitants: change in routine, roommate, caregiver, overstimulation/under-stimulation, other disruptive patients, family illness Clinical Evaluation- History Periodic testing with either MMSE or Clinical Dementia Rating (CDR) Draw-a-Clock test Consider neuropsych testing Testing must be socially relevant and appropriate for level of education Clinical Evaluation- Workup? Labs: Less than 1% yield AmerAcadNeurology suggests only TSH, B12 If Hxand exam indicate, RPR, CBC, CMP, heavy metals, Utox, CSF studies Neuroimaging: YES x1 NoncontrastCT or MRI of brain Can reveal CVD, neoplasm, hematoma, nl pressure hydrocephalus, also define areas of atrophy. Neurology. 2001;56(9):1143 Treatment basics: Treat underlying medical illness Correct sensory deficits Remove offending medications Keep environment comfortable, calm, homelike Regular daily activities, exercise and structure Assess sleep and eating patterns Educate and support caregiver Cholinesterase Inhibitors Mech: Inhibit Ach breakdown in brain Donepezil (Aricept ) qd* Less systemic anti-ach side effects Rivastigmine(Exelon ) BID Smidge better, best side effect profile Galantamine(Razadyne ) BID Better when mild mod dementia (MMSE 10-26) Cholinesterase Inhibitors Start low and go slow Most effective at highest doses but sideeffects increase too and can limit use. In the case of Alzheimer s disease improvement = slower decline May need addlmedications to address other sx: mood, agitation, sleep. However, dilemma of polypharmacy Goodol UpTo Date 2012 Ann Intern Med. 2008;148(5):379. 2
Cholinesterase Inhibitors SystRev mild improvement in cognition and global fxn, studies ~ 6 mos, no overall QOL difference However, 30-50 % ptsmay show NO improvement Start with 8 week trial then re-assess Other pharma: Memantine(Namenda ) inhibits glutamate which acts as neurotoxin May help in later stages of AD Often added to anticholinesterase inhibitor Statins? Rotterdam study (n = 6992) Retrospective study cp statin users to never used.. HR 0.57 Degree of lipid improvement did not matter Animal studies show statins decrease level of amyloid protein in brain. However, Cochrane review of subsequent RCT s did not support. Statins started too late? J Neurol Neurosurg Psychiatry. 2009;80(1):13. Cochrane Database Syst Rev. 2009 Gingko biloba RCT of 120 mg BID ginkgo cp to placebo N = 3000 pts, age 75 or older Followed up from 2001-2008 No difference in rate of decline to AD Again, Rx started too late? JAMA. 2008;300(19):2253 JAMA. 2009;302(24):2663 Role of Prevention Prevention: Diet Mediterranean Diet (MeDi) --those with highest adherence had reduced risk of AD. Cplowest to Med tertile: HR 0.85 Cplowest to High tertile: HR 0.60 (n = 2258) MeDi also helps prevent mild cognitive impairment, 17 28% less risk over 4 years. (n = 1393) Ann Neurol. 2006;59(6):912. (MeDi diet) Arch Neurol. 2009;66(2):216. 3
Prevention: Diet Daily consumption of V/F showed reduced risk, HR 0.72. Weekly fish consumption ~ HR 0.65 High omega 6 intake hazard ratio of 2.12 in high risk genetic group (Apo E epsilon 4 noncarriers) Healthy combo of F, V, nuts, poultry, fish showed HR 0.62 cpto red meat, butter, high fat dairy. Omega 3: DHA levels Framingham Heart Study. A prospective study n = 899 men and women, free of dementia at baseline, at mean 9.1 years Top quartile of plasma PC DHA showed 47% reduced risk of developing dementia of all causes Neurology. 2007;69(20):1921 Arch Neurol. 2010;67(6):699. Schaefer EJ, Arch Neurol. 2006 Nov;63(11):1545-50. Physical exercise & movement Crude cumulative incidence of dementia in subjects with baseline plasma phosphatidylcholine docosahexaenoic acid (PC DHA) levels in the upper quartile compared with those with levels in the lower 3 quartiles. Aerobic conditioning Increases cerebral blood flow Slows development of AD National Long-Term Care Study OR 0.55 to 0.30 10 years f/u Walking (average 5x/week) and gardening (2-3x/week) most frequent activities Best if 20 minutes or longer Neurology 1998; 50:A89-A90. Alzheimers Dement 2010; 6:448-455. Physical Exercise RCT 24-week physical activity intervention vs education N=138, aged 50 years or older, mild cognitive dysfunction 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period Intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog versus 0.04 points in controls Lautenschlager NT, JAMA. 2008 Sep 3;300(9):1027-37 4
Cognitive fitness Cognitive stimulation Music, art, crossword puzzles, headline discussion Mental training Can increase neuron dendrite sprouting Addlbenefit of social time with others J Neurosci Res 1975; 1:109-119. Hormone Replacement Rx DHEA Pregnenolone Estrogen? -- Huperzine A Natural anticholinesterase inhibitor from Chinese club moss Animal studies: surpassed effects of donepezil (Aricept ) in reversing memory deficits Low side effect profile Dose: 50 mg qd-bd Khalsa DS, Alzheimer Disease in Rakel, ed Integrative Medicine, 3 rd edition Meditation May mediate effects of chronic stress Cortisol cascade, affects hippocampus which regulates cortisol feedback Hippocampus volume inversely related to cortisol Meditators have less lipid peroxidase, higher DHEA, lower cortisol Lupien SJ et al. Nat Rev Neurosci 2009; 10:434-445. Horm Behav 1978; 10:54-60 Wallace RR. The Physiology of Consciousness. J Alzheimers Dis 2010; 20:517-526 Kirtan kriya Kirtan Developed by Yogi Bhajan SaaTaaNaaMaa 3 rd eye focus Mudras fingers 2,3,4,5 Cerebral blood flow changes during chanting meditation. Nucl Med Commun 2009; 30:956-961. 5
Pearls Definition: Memory impairment + other cognitive decline & impairs daily living REVIEW MEDS! Inquire about alcohol Obtain objective testing MMSE or other Caregiver support is critical. All Rx after horse is out of barn = minimal efx PREVENTION IS KING! DO recommend anti-inflmdiet, exercise, stress reduction, social connection. 6