638 a target INR >3 is effective in reducing thrombotic recurrences. Treatment during pregnancy includes both aspirin and heparin. NB: Hypercoagulable studies performed at the time of a thrombosis can be misleading because of alterations of clotting factors due to acute illnes s or the thrombosis itself and should be avoided. y g o o t a m e H l Immunosuppressive drugs Immunosuppressive drugs are used in organ and marrow transplants, r heu- matoid arthritis, psoriasis, chronic hepatitis, asthma, giant cell arteritis, polymyal gia, SLE, PAN, and inflammatory bowel disease and many other autoimmune diseases. Prednison e Steroids can be life-saving, but a number of points should be taken into consideration be fore initiating treatment. \212 Hypertension, osteoporosis, and diabetes may be exacerbated by steroids. Do not stop steroi ds suddenly. Adrenal insufficiency may result, as endog- enous production takes time to res tart (p. 312). Increase steroid dosing at times of illness/stress (e.g., flu or preop). Min imize side effects by using the lowest dose possible for the shortest amount of time. Give doses in the morning, and alternate days if possible, to minimize adrenal suppression. Befo re starting steroid treatment, extensively counsel your patient regard- ing the risks and b enefits of steroids and the impact of steroids on their comorbidities. Avoid concurrent dru gs bought over the counter (e.g., aspirin, ibuprofen); the danger is steroid-associated GI bleeds: If NSAIDs are essential ask the patient to come to you for advice. You might consid er an NSAID com- bined with misoprostol, a prostaglandin analog. Interactions: Antiepilepti cs (below) and rifampin. Strongly consider pneumocystic pneumonia (PCP) prophylaxis in pati ents who are on other chemotherapeutic regimens, who require moderate steroid dosing for lo ng periods of time, or in patients who are otherwise immunocompromised. \212 \212 \212 \212 \212 \212 \212 \212SE: TB reactivation, edema, osteoporosis, cataracts, euphoria, elevated glucose, Pneum ocystis , urinary tract infection (UTI), toxoplasmosis, asper- gillus, serious chicken pox/ zoster, so avoid contacts (and so the need for varicella zoster immunoglobulin). Avoid preg nancy. \212 Azathioprine SE: Peptic ulcer, marrow suppression, reduced WBC. Do CBCs. Interactions : Mercaptopurine and azathioprine (which metabolized to mercaptopurine) are metabolized by xanthine oxidase (XO). Azathioprine toxicity results if XO inhibitors (allopurinol) are coa dministered. Genotype testing for thiopurine methyltransferase (TPMT) should be done prior to initiating azathioprine. Patients with low enzyme activity have increased risk of toxici ty. Cyclosporine Transplant patients usually require 6 mg/kg/d; in other patients, keep the dose <4 mg/kg/d. Monitor urine (UA) and creatinine every 2 wks for the first 3 months, the n monthly if dose >2.5 mg/kg/d (every 2 months if less than this). Reduce the dose if creat inine rises by >30% on two measurements even if the creatinine is still in the normal range . Stop if the abnormality persists. Monitor blood levels in transplant patients. SE: Nephro toxicity, hepatotoxicity, edema, gum hyperplasia, tremor, paresthesia, hypertension, confus ion, seizures, lymphoma, skin cancer. Interactions are legion. Cyclosporine levels are incr eased by ketoconazole, diltiazem, nicardipine, verapamil, oral contraceptives, erythromycin . Cyclosporine levels are reduced by barbiturates, carbamazepine, phenytoin, rifampin. 639 Avoid concurrent nephrotoxics: Gentamicin, amphotericin. Concurrent NSAIDs augment nephroto xicity: Monitor LFTs. Methotrexate Inhibits dihydrofolate reductase, which is involved in t he synthesis of purines and pyrimidines. SE: Hepatitis, lung fibrosis, CNS signs, teratogen icity. Methotrexate \200\231s action is increased by NSAIDs, aspirin, penicillin, probeneci d. Cyclophosphamide SE: Carcino- and teratogenic, hemorrhagic cystitis, marrow suppression. 640 This page intentionally left blank Geriatric medicine Colleen Christmas , M.D. e n i c i d e m c i r t a i r e Contents What is special about geriatric patients? 642 The elderly patient in the hospital 642 Frail ty, falls, and postural hypotension 644 Impairment, disability, and stroke rehabilitation 6 45 Urinary incontinence 646 Polypharmacy 648 Examination of mental state 648 Approach to de mentia 649 Alzheimer dementia 651 Preventive geriatrics 651 G What is special about geriatric patients? Many aspects regarding older adults make them a c hallenging and rewarding patient population to work with. Most of the care of older adults consists of simultanous management of multiple chronic diseases. The course of their medica l conditions will be punctuated by episodes of exacerbation of acute illness. With each suc cessive exacerbation, prognosticating the amount of recovery becomes increasingly difficult . Another challenge in providing care to geriatric patients is that quality of life, risks of treatment, and functional disability take on greater importance in making treatment deci sions. Geriatric patients represent an incredibly heterogeneous group demograph- ically and physiologically. From person to person the effects of lifestyle, genetic, and environmenta l factors produce variable results in aging of dif- ferent organ systems. While one octogen arian may be active, driving, caring for grandchildren, and have well-controlled chronic co nditions, the next may be severely debilitated, dependent on others for most of his or her care needs, and profoundly cognitively impaired. Thus, the approach to geriatric patients m ust be highly individualized. The final principle to be considered in caring for older adul ts is that of intrinsic vulnerability. Although exercise may ameliorate some of the adverse effects of aging on most organ systems, even the very healthy aged suffer from a reduced a bility to withstand physiologic perturbation. Examples of this may include glucose metaboli sm that appears normal during usual situ- ations but becomes abnormal with mild disturbance , such as a urinary tract infection. This dictates a requirement to \200\234stay on your t oes, \200\235 treat gingerly, and frequently reassess the impact of interventions in geriat ric patients. 6 1 The elderly patient in the hospital It is only in the past 200 yrs that life-expectancy has risen much above 40 yrs. An aging population is a sign of successful social, health, and e conomic policies . Beware of ageism. Old age is associated with disease but doesn \200\231t cause it. Any deterioration is from treatable disease until proven otherwise . \212 642 Contrary to stereotype, most old people are independent. 95% of those >65 yrs and 80% of th ose >85 yrs old do not live in institutions; about 70% of the latter can manage stairs and can bathe without help. \212 With any problem, find the cause; resist temptation to think: This is simply aging . Look ( within reason) for treatable disease, especially medication adverse effects, \206\223 fitn ess, and social factors. Do not restrict treatment simply because of age. Old people vary. Age alone is a poor predictor of outcome and should not be used as a sub- stitute for caref ul assessment of each patient \200\231s potential for benefit and risk. e n i c i d e m c i r t a i r e G \212 Characteristics of disease in old age There are differences of emphasis in the approach to old people compared with young people. \212Multiple pathology: Several disease processes m ay coincide: Find out which impinge on each complaint (e.g., senile cataract + arthritis = falls). \212Multiple causes: One problem may have several causes. Treating each alone may do little good; treating all may be of much benefit. \212Nonspecific presentations: Some presentations are common in old people: Incontinence, immobility, instability (falls), weight loss, and delirium/ confusion. Any disease may pres ent with these. Also, typical signs and symptoms may be absent (myocardial infarction [MI] without chest pain; pneumonia, but no cough, fever, or sputum). \212Rapid worsening if treatment is delayed: Complications are common. Often a muted prese ntation, such as excess sleepiness, may belie a life-threatening disease, such as acute MI. \212More time is required for recovery: Impairment in homeostatic mechanisms leads to loss of physiological reserve. \212Impaired metabolism and excretion of drugs: Doses may need lowering, both because of d eclines in liver and kidney function with aging and because there is often less tolerance t o side effects. \212Social factors: These are central in aiding recovery and return to home. Special points in caring for the elderly In the history: Assess all disabilities, then: \212Home details : E.g., stairs; access to toilet? \212Medication : What? When? Assess und erstanding and concordance. How many different medications can they cope with? Which are th e most important drugs? You may have to ignore other desirable remedies or enlist the help of a friend, spouse, or pharmacist (who can batch morn- ing, noon, and night doses in compa rtmentalized containers so complex regimens may be reduced to \200\234take the morning com partment when you get up, the noon compartment before lunch, etc. \200\235). \212Social network : Regular visitors; family and friends \212Care details : What service s are available (meals delivered, home care nurse, community psychiatric agency, physical t herapist)? Who else is involved in the care? Speak to others (relatives, loved ones, neighb ors, caregivers, personal physician). See Table 16.1. On examination: \212 Do blood pressure (BP) readings lying and standing (postural hypoten- sion may lead to fall s). Rectal exam: Impaction may lead to overflow incontinence. Watch the patient walk; this is a good way to assess balance, strength and coordination simultaneously and also determin e if the patient is safe to return to home independently or may benefit from a stay in reha bilitation. Detailed central nervous system (CNS) examination is often needed (e.g., if pre sentation is nonspecific). 643 \212 \212 \212 Table 16.1 Beyond the hospital: Planning successful discharges Start planning discharge from day 1. A very common question on rounds is: \200\234Will thi s patient do OK at home? We \200\231ve got them as good as we can, but is discharge safe? \200\235 In answering this, take into account: \212 \212 \212 \212 Most patients want to go home promptly. If not, find out why. Is the home suitable for a fr ail person? Stairs? Toilet on same floor? If toilet access is difficult, can they transfer from chair to commode? Can they open a can, use the phone, turn on a microwave, cook soup? Does the patient live alone? Does the caregiver have family support? Is he or she already e xhausted by other duties (e.g., young children at home)? Is the family supportive \200\224i n theory or in practice? Are the neighbors friendly? Are social services and community geri atric services well integrated? Proper case management programs with defined responsibiliti es, entail- ing integration of social and geriatric services, really can help. \212 \212 \212 \212 \212 Make a care plan: \212 \212 Include nutrition. Is the patient able to eat the food that is delivered? Involve a multidi sciplinary team. Including nonphysician health care pro- fessionals. Their expertise can ma ximize the treatment plan. Frailty, falls, and postural hypotension Frailty is a syndrome that best incorporates the n otion of increased vulner- ability to insults and subsequent exaggerated effects of insults . A phenotype has been described 1 in which three or more of five recognized characteris- t ics describe this syndrome: \212 \212 \212 \212 \212 Studies demonstrate that frailty is associated with aging and is associated with higher rates of health care utilization, di sability, and mortality. The biologic mechanisms contributing to the development of frailty are just beginning to be unraveled, with the hopes that discovery of such mecha- nisms wil l lead to interventions that favorably alter the clinical course. Unintended weight loss of Poor grip strength Self-reported poor endurance and exhaustion Sl ow walking time Low physical activities level \211 10 pounds over the previous 12 months Falls are common (30% of those >65 who live in the community fall in a year), and this may be the start of a fatal course of events. There are many causes. 10% are related to loss of consciousness or dizziness. For most, there is no clear single cause, and many factors con spire. History: Exact circumstances of fall. Find out about any CNS, cardiac, or musculoske letal abnormalities. Drugs causing postural hypotension; seda- tion; arrhythmia, parkinsoni sm (e.g., tricyclics, neuroleptics, including meto- clopramide and prochlorperazine, as wel l as alcohol). Examination: For causes: Postural hypotension; arrhythmias; detailed neu- ro logical examination, including cerebellar signs, parkinsonism, proximal myopathy, gait; wat ch patient get up from chair; test for Romberg \200\231s sign; mechanical instability in kn ees or feet. 644 Consequences: Cuts; bruises; fractured ribs ( pneumonia) or limbs, espe- cially of femur; head injury ( subdural hematoma). Often patients who fall significantly restrict activit ies because of intense psychological fear of falling. Management: The patient \200\231s con fidence may be shattered even if there is no serious injury. Look for causes and treat. Con sider physical therapy; include learning techniques on how to get up from floor. Occupation al therapists may advise on reducing household hazards and adding aids. Exercise and balanc e training can prevent falls. Postural hypotension is important because it is common and a cause of falls and poor mobility. Typical times are after meals, on exercise, and on gettin g up at night. May be transient with illness (e.g., flu). Causes: Leg vein insufficiency, a utonomic neuropathy, drugs (diuretics, nitrates, antihypertensives, antidepressants, sedati ves). Red cell mass may be low. Management : Reduce or stop drugs if possible. Counsel pati ent to stand up slowly in stages. Try compression stockings. Reserve fluid-retaining drugs (fludrocortisone 0.1 mg PO daily, \206\221 as needed) in those severely affected when othe r measures fail. e n i c i d e m c i r t a i r e G Impairment, disability, and stroke rehabilitation Doctors are experts at diagnosing disease and identifying impairment. But we are slow to see the patient \200\231s perspective. Cons idering the concepts of impairment and disability may help. Impairment refers to systems or parts of the body that do not work. \200\234Any loss or abnormality of psychological, phy siological or anatomical structure or function. \200\235 For example, following stroke, par alysis of the right arm or aphasia would be impairment. Disability refers to things people cannot do. \200\234Any restriction or lack (resulting from an impairment) of ability to pe rform an activity in the manner, or within the range, considered normal for a human being. \200\235 For example, following stroke, difficulties in \200\234activities of daily living \200\235 (e.g., with dressing, walking). Making use of these distinctions Two people with the same impairment (e.g., right hemiparesis) may have different disabilities (e.g., one ab le to dress, the other unable). The disabilities are likely to determine the quality of the person \200\231s future. Treatment may usefully be directed at reducing disabilities. For example, Velcro fasteners in place of buttons may enable a person to dress. Three stages of management Assessment of disability: Traditional \200\234medical \200\235 assessment focuses on disease and impairment. Full assessment requires a thorough understan ding of dis- ability. Discuss detailed assessments with expert therapists, the patient, and relatives to help define their problems. Who can help? Hospital doctors are part of a larg e team. Involve other members of the team early, including nurses, occupational and physica l therapists, social workers, and the primary care physician. Also, there are self-help org anizations for most chronic diseases aimed both for patients and their caregivers. Generate solutions to problems: A list of disabilities is the key. Rehabilitation should look at ea ch disability (e.g., unable to undress). Uncover the origin of the disability (in terms of disease and impairment). Mutual goals should 645 be agreed upon with the patient and relatives in accordance with their wishes. At every vis it, review, renew, and adapt goals. Rehabilitation after stroke Good care consists of attention to detail. The principles of re habilitation are those of any chronic disease and are best carried out in specialist inpa- tient stroke units (they reduce morbidity and institutionalization). Special points in earl y management: Watch the patient drink a glass of water: If they cough or gag, they should b e kept NPO for several days. Maintenance IV fluids should (almost) always be ordered at the same time as making someone NPO. The optimal use of nasogastric (NG) and per- cutaneous en doscopic gastrostomy (PEG) tubes is controversial, although a randomized clinical trial dem onstrated no benefit compared to NPO in the first week after a dysphagic stroke. Consider c onsulting with the speech and swallowing service. Avoid injuring the extremities of patient s through careless lifting. Ensure good bladder and bowel care through frequent toileting. Avoid early catheterization, which may prevent return to continence. Position the patient t o minimize spasticity. Urinary incontinence Incontinence is never normal although it occurs in up to 30% of the el derly at home and 50% in long-term care. It is transient in 30% \200\22340% of patients, an d the causes are multiple and frequently coexist. Intrinsic urinary tract malfunction can r esult in detrusor overactivity , involuntary contractions of the bladder; detrusor underact ivity , failure of adequate bladder contraction; stress incontinence , abnormally low ureth ral resistance; or obstruction , abnormally high urethral resistance. Causes of transient i ncontinence are often (but not always) outside the urinary tract. Remember \200\234 DIAPPE RS \200\235 : D elirium; I nfection of the urine (not asymptomatic bacteruria); A trophic u rethritis and vaginitis (responds to estrogen); P harmaceuticals (sedatives, anticholinergi cs, antipsychotics, antidepressants, narcotics, -adrenergics, diuretics, angiotensin-con verting enzyme [ACE]-inhibitors), P sychological (severe depression), E xcess urine ( \206 \221 input; \206\221 production \200\224diuretics, EtOH, \206\221 glucose, \206\221 calc ium; mobilized peripheral edema), R estricted mobility (arthritis, pain, gait disorders), S tool impaction. Points in the history Urgency (the abrupt need to void or a spontaneous em ptying of the bladder without warning) suggests detrusor overactivity. Leakage during stres s maneuvers (e.g., coughing, laughing, sneezing) suggests reduced urethral resistance. Pros tatism suggests obstruction. Ask about other medical illnesses \200\224cancer, diabetes mel litus (DM), urinary tract infections (UTIs), H/O pelvic radiotherapy (XRT). A 2 \200\2237-d voiding diary is useful, both to understand the pattern of incontinence and as a baseline to compare treatment outcomes. The patient should record the time, volume, situation, and a ssociated symptoms whenever urine is passed. Physical examination A comprehensive physical examination is vital. Look for abnormal affect, functional impairment (e.g., \206\223 mobi lity, vision, etc), congestive heart failure (CHF), orthostasis, peripheral edema, atrophic vaginitis. Test perianal sensation and reflexes (anal wink, S4 \200\2235; bulbocavernosus, S2 \200\2234). Do a rectal exam for resting and voluntary anal tone, fecal impaction, and prostate enlargement. The cough stress test is useful (especially in women). Check the post void residual (PVR) by in/out, 646 \200\234straight \200\235 catheter, or ultrasound estimation after a voluntary void (norma l: <50 \200\223100 mL). Investigations Chemistry panel, Ca 2+ , urinalysis, and culture. In selected patients, consider renal US, urine cytology, urodynamic studies. Treatment is aim ed at the cause. Specific measures may include altered timing of medications, compression s tockings during the day to reduce nocturnal mobilization of edema, and behavioral technique s such as frequent voiding (e.g., q2 \200\2233h; refer to the voiding diary for guidance) t o avoid bladder overdistension and involuntary contraction. Pelvic floor or \200\234Kegel \200\235 exercises (voluntary contraction of the external urethral sphincter for 10 sec \227 50/d) can help stress incontinence in women. Drugs with anticholinergic or -adrene rgic antagonist activity may be useful (see Table 16.2). Surgery, prostheses (e.g., penile clamps), intravaginal pessaries, external collecting devices (indwelling or condom catheter s), and absorbent pads are reserved for refractory incontinence. Complications Perineal ras h, decubitus ulcers, indwelling catheters and UTIs, social stigmatization, anxiety/depressi on, \206\223 sexual activity, institutionalization. Drugs for urinary incontinence Start w ith the lowest dose, then titrate up until symptoms improve or intolerable side effects dev elop. The expected benefits are small. e n i c i d e m c i r t a i r e G Table 16.2 Medications For the Treatment of Urinary Incontinence Detrusor overactivity: Propantheline Oxybutynin Imipramine 7.5 \200\22330 mg PO 3 \200\2234 times a day 2.5 \200\2235 mg PO 3 \200\2234 times a day 25 \200\22350 mg PO 1 \200\2233 times a day Tolterodine Darifenacin Fesoterodine Solifenacin Trospium 1 \200\2232 mg PO bid 7.5 \200\22315 mg PO daily 4 \200\2238 mg PO daily 5 \200\22310 mg PO daily 20 mg PO bid Stress incontinence: Phenylpropanolamine 25 \200\22350 mg PO 2 \200\2233 times a day Outlet obstruction Prazosin Phenoxybenzamine 1 \200\2232 mg PO 2 \200\2234 times a day 5 \200\22310 mg PO daily (for short-term use only ) 647 Tamsulosin Dutasteride Doxazosin Terazosin Alfuzosin Silodosin Finasteride 0.4 mg PO daily 0.5 mg PO daily 1 \200\2238 mg PO daily 1 \200\22310 mg PO daily 10 mg PO d aily 8 mg PO daily 5 mg PO daily Polypharmacy Geriatric patients disproportionately consume prescription and nonpre- scripti on medications. Additionally, geriatric patients have poorer tolerance for adverse drug eff ects and more commonly suffer from the harms of medications than their younger counterparts . Thus, trying to minimize the total number of drugs consumed is both a laudable and formid able goal. Drugs that should be avoided because safer alternatives exist include cyclo-oxyg enase (COX)-2 inhibitors and non-COX-specific NSAIDs and meperidine. Benzodiazepines and no nbenzodiazepine sleeping agents should be avoided for insomnia as they substantially increa se the risks of falls and confusion. Drugs to treat Alzheimer \200\231s disease (AD) have d emon- strated little, if any, meaningful clinical benefit; their use should be con- sidered carefully as a trial in an individual. Atypical antipsychotics do not offer benefit over o lder, less expensive agents for behavioral problems in dementia. Finally, any new drug must also be very carefully considered. In seeking FDA approval for release, most drugs have no t been tested on the average geriatric patient with multiple comorbidities and medications. Most certainly, they have not been tested on the frailest elderly. Only after a drug has b een on the market and used in large numbers of \200\234average \200\235 people do many of the serious toxicities become apparent. Many elderly are seriously injured as the result of new medications. Adhere to the adage, \200\234start low, go slow \200\235 with any new me dicine. Costs, ability to take, and potential toxicity are important determinants in select ing drugs. Opportunities to get \200\234double duty \200\235 from medications should be ex plored. For example, a person with neuropathic pain and depression may derive good benefit from nortriptyline at bedtime for both of these problems, rather than gabapentin three time s a day and an selective serotonin reuptake inhibitor (SSRI) once a day. Finally, the selec tion of medications must consider the overall treatment goals for each individual and wheth er or not data exist that the considered medication will reasonably further those goals. Examination of mental state The examination of cognitive functions is important in every pa tient. Much can be accomplished by careful observation during the course of the history and physical examination. For more detailed assessment of specific cognitive functions, you sh ould have a set of questions (and tasks) with which to test the patient. Use these whenever an altered mental state is contributing to the clinical problem. A description of each of the tests performed, and the patient \200\231s response, is more useful for the clinical re cord than a \200\234score \200\235 on a question set. Before starting, tell the patient th at you are going to test his thinking. Reassure him that it is a standard part of the exami nation. Components of the mental state examination Level of arousal: E.g., alert, drowsy, asleep bu t responds to voice/touch/ gentle shake/pain. Rouses for x seconds, then falls back to slee p. Orientation: Ask the patient \200\231s name, the place where you are located, and the ti me (day of the week, date, month, year, season). Attention: Recite months of the year forwa rd and backward. If unable, try days of the week, the word \200\234world. \200\235 Memory: Distant: Names of children, where they grew up, jobs. Recent: Describe news events, detail s of recent illness, dinner last night. Learning: Give three objects to remember (e.g., \200\234glass, a duck, and a shoe \200\235). Make 648 sure they can repeat them without prompting after a 30 sec delay without distractions. Ask them again in 3 \200\2235 min (don \200\231t forget!). Speech: Fluency, naming, repetition, comprehension. Calculation: Serial 7 \200\231s. How many quarters in $1.50? Nickels in $1. 10? Simple addition, multiplication, etc. Reading: Read aloud (e.g., lunch menu), then desc ribe what they read. Writing: Write a sentence, e.g., about the weather. Construction: Draw the numbers inside a circle as if it were a clock. Copy intersecting pentagons. Copy a cub e. Left/right discrimination: Praxis: Salute. Pretend to comb, roll dice, deal a pack of ca rds. \200\234Frontal \200\235 functions: Copy a sequence of three hand movements; Go/No-go task : \200\234Every time I tap my hand twice, you tap once. When I tap once, you do noth ing. \200\235 Word lists : \200\234In one minute, tell me all of the words that you can th ink of that begin with the letter F . \200\235 Cortical sensation: Graphesthesia: Ask the p atient to identify numbers, drawn in each palm. Stereognosis: Identify objects (e.g., comb, fourth, nickel, pen) placed in each hand without looking. Note : These terms refer to norm al functions. \200\234Agraphesthesia \200\235 and \200\234astereognosis \200\235 are abno rmal. Sometimes a complex multidimensional question can be used as a screening test for cog nitive dysfunction. For example: \200\234Pretend that you are looking at a clock. The litt le hand is on the 7 and the big hand is on the 3. What time will it be in 15 minutes? \200 \235 A correct response on this task ( \200\2347:30 \200\235) requires many faculties, incl ud- ing attention, language comprehension, calculation, visual memory, and construction. In selected patients, in whom mental state is not the issue, this may be sufficient to satisf y yourself that there are no gross cognitive abnormalities. Never document that the mental status is normal unless you have tested it. e n i c i d e m c i r t a i r e G Approach to dementia An altered mental state is due to a treatable illness until proved oth erwise. Dementia is not a part of normal aging. It is a syndrome \200\224with many causes \200\224of progressive impairment of cognition with the preservation of clear consciousness . Clinical features The key to diagnosis is a good history (usually requiring an informant) o f progressive impairment of memory and other cognitive functioning, together with objective evidence of such impairment. The history should go back at least several months and usuall y years. Typically, the patient has become increasingly forgetful and has performed normal tasks (e.g., cooking, shopping, finances, work) with reduced competence. Sometimes the pati ent appears to have changed personality (e.g., uncharacteristically rude or aggressive). Po ints in the history: \212 \212 \212 \212 \212 649 Baseline personality, education, profession Duration of illness Onset (abrupt or insidious) Comorbid disease Past medical history: Poor nutrition, head trauma, depression or other ps ychiatric illness Medications (including PRNs) Toxins (occupational, EtOH) \212 \212 \212 \212 Risk factors for infections(HIV, syphilis) Family history of depression, dementia, or other degenerative disease Epidemiology Incidence increases with age. Very rare in those <55 yrs. 5 \200\22310% preval ence >65; up to 50% >85. In the United States, there are 4 million people with AD, at a co st of $90 billion/yr. Causes Definitive diagnosis requires a pathological specimen (biopsy or autopsy). Premorbid diagnoses are often mistaken. AD is the most common cause of dement ia (55 \200\22370% of all cases). Vascular dementia comprises 5 \200\22325% of all cases; e ssentially, multiple small strokes. Usually evidence of vasculop- athy (high BP, previous s trokes); sometimes of focal neurological damage. Onset sometimes sudden, and deterioration may be \200\234stepwise. \200\235 Optimize vascular risk factors to try to prevent further progression of disease. Lewy body disease is characterized by Lewy bodies in the brainstem and cortex. There are fluctuating but persisting cognitive deficits, parkinsonism, and hal lucinations. Less common causes HIV ( not uncommon in those known to have HIV), progressive multifocal leukoencephalopathy, Pick \200\231s disease, progres- sive supranuclear palsy, Parkinson \200\231s disease, Jakob-Creutzfeldt disease, Huntington \200\231s disease, Werni cke \200\223Korsakoff disease. Initial assessment For all patients with progressive dementi a: Careful his- tory (as above); CNS exam (including mental state); CBC, erythrocyte sedi- mentation rate (ESR), chemistry, thyroid-stimulating hormone (TSH), B 12 , syphilis serolog y, drug levels; computed tomography (CT) or magnetic res- onance imaging (MRI) of the brain . For selected patients: Neuropsychology testing, psychiatric examination, electroencephalo gram (EEG), HIV testing, liver profile (LP), toxic screen. Management Treat any treatable c ause. Treat concurrent illnesses (these may contribute significantly to confusion). In most people, the dementia remains and will progress. Involve relatives and social services. Pot entially treatable dementias The frequency of reversible dementias that present to memory s pecialists is somewhere between 0% and 30%. The reason to investigate dementia is to find o ne of the causes that can be fixed. Drug toxicity: Check all medications. Chronic metabolic disturbance: Organ failure (heart, kidney, liver, lungs), Wilson \200\231s disease, obstru ctive sleep apnea, dialysis encephalopathy (?alumi- num toxicity), heavy metals (e.g., lead ). Normal pressure hydrocephalus is thought to be due to impaired cerebro- spinal fluid (CS F) absorption, causing dementia, gait apraxia, and urinary incontinence. Disproportionately large ventricles on CT/MRI. Diagnosis is difficult to confirm, although some patients bene fit from CSF shunts (e.g., ventriculoperitoneal). Good prognosticators for response to shun ting include short duration of symptoms, more prominent gait disorder than dementia, known etiology (e.g., history of subarachnoid hemorrhage, head trauma), altered CSF dynamics (wit h invasive monitoring). Intracranial mass: Tumors (especially meningiomas), subdural hemato ma. Infection: Syphilis, Lyme, chronic meningitis (tuberculosis [TB], fungal, parasitic). C onnective tissue disease: SLE , sarcoidosis, primary angiitis of the CNS and other vasculit ides. Endocrine: Hypo-/hyperthyroidism, parathyroid, adrenal and pituitary dis- ease, insul inoma. Nutritional: Deficiencies of B 12 , nicotinamide (pellagra), thiamine. Psychiatric: Pseudodementia of depression. 650 Alzheimer dementia This is often considered the worst neuropsychiatric disorder of our time s. Suspect AD in adults with any persistent, acquired deficit of memory and cognition; e.g. , as revealed in the mental test score and other neuropsy- chometric tests. Onset may be fr om 40 yrs (or earlier; e.g., in Down \200\231s syn- drome), so the notions of \200\234seni le \200\235 and \200\234presenile \200\235 dementia are irrelevant. Diagnosis is often hap hazard. Specialist assessment with neuroimaging for all would be ideal (this would help rul e out frontal lobe and Lewy body dementias, and Pick \200\231s disease). Histology (rarely used) \212 e n i c i d e m c i r t a i r e G Deposition of in the amyloid precursor protein) Neurofibrillary tangles and an increased nu mber of senile plaques \200\223 amyloid protein in cortex (a few patients have mutations \212 Presentation Early (stage I) in AD, there is failing memory and spatial disorientation. In stage II (follows after several years), personality changes (e.g., increased aggression and focal parietal signs \200\224dysphasia, apraxia, agnosia, and acalculia). Parkinsonism may occur. In stage III, the patient becomes apathetic, wasted, bedridden, and incontinent. Se izures and spasticity are common. Mean survival 7 yrs from onset. Management Theoretical is sues: Potential strategies: \212 \212 Preventing the breakdown of acetylcholine (e.g., donepezil; see below) Augmenting nerve gro wth factor (NGF), which is taken up at nerve end- ings and promotes nerve cell repair Stimu lating nicotinic receptors that may protect nerve cells Inhibiting the enzymes that snip-ou t cursor protein (APP), so preventing fibrils and plaques Using anti-inflammatories to prev ent activation of microglial cells to secrete neurotoxins (e.g., glutamate, cytokines), whi ch stimulates forma- tion of APP Regulating calcium entry (mediates the damage of neurotoxi ns) Preventing oxidative damage by free radicals \212 \212 \200\223 amyloid peptide from amyloid pre- \212 \212 \212 Practical issues: Treat concurrent illnesses (they contribute significantly to confusion). In most people, the dementia remains and will progress. Involve relatives and c ommunity services. Consult with an expert; if the dementia is mild or moderate, consider in creas- ing acetylcholine availability by inhibiting acetylcholinesterase (e.g., donepe- zil 5 mg PO every night at bedtime; increasing to 10 mg after 1 month). Effects may be minimal , but subtle cognitive changes can cause significant behavioral improvement even without \200\234objective \200\235 improvement in bedside tests of cognition. The need for institut ional care may be delayed. Prevention There are no clear ways to avoid this disease. Hormon e replacement therapy (HRT) and controlling vascular risk factors may offer some protection . 651 Preventive geriatrics Although even the most fit elderly will have continued declines in mo st organ systems with aging, evidence clearly supports that exercise can ame- liorate many of these losses substantially and help preserve function and independence. It may help impr ove range of movement and decrease pain associated with knee osteoarthritis. It has been sh own to both treat osteo- porosis and, in retrospective studies, prevent it. Exercise, parti cularly exer- cises that incorporate some aspect of balance training, have been shown to re duce falls, even in high-risk individuals. As with their younger counterparts, exercise may lower BP and favorably alter lipid profiles. Clearly, the most fit individuals tend to have the longest life expectancy and longest period of functional independence. Ep idemiologic studies demonstrate that improving fitness state is associated with beneficial effects on mortality, even when this change is enacted in older age. Although the best exer cise regimen has not been firmly established, most elderly are remarkably sedentary and wil l gain substantially simply from reducing their inactivity by altering lifestyle. Examples of this include watch- ing less television, taking the stairs rather than the elevator, par king farther away from the entrance of stores, and walking up and down every aisle in the g rocery store. Walking is an inexpensive exercise that has functional rel- evance. The physi cian may assist in improving fitness by endorsing exercise and identifying barriers and fac ilitators to exercise with patients. Most authorities endorse screening examinations for ol der individuals similar to those of younger individuals when the projected life expectancy is >10 yrs and when such screening (and subsequent decisions based on the results) is consi stent with the overall goals of care of the individual. Although accurate prognosis is extr emely difficult in patients with severe chronic conditions that exacerbate and remit, some evidence suggests that most physicians tend to underestimate life expectancy in the elderly when considering these decisions. Be particularly cautious of the risk of ageism. For exam ple, the life expectancy of an 85-yr-old woman who is in the top quartile of functional sta tus is nearly 10 yrs. Screening decisions about patients with cognitive impairment are part icularly vexing and must take into careful consideration the ability of the patient to part icipate in the test- ing, the risks of such testing, the ability of the patient to undergo treatments if a disease is found, and, most important of all, the overarching goals of care . Prevention of injury in the elderly would include assessment for falls; discussions about firearms, particularly if a demented individual is in the home; use of seat belts in cars; evaluation for continued ability to drive; and home safety assessment. Smoking cessation r educes the risk of lung cancer at any age. Although not proven for primary prevention of co ronary artery disease (CAD), it continues to have an important role in prevention of MI in patients with established CAD. Thus, cessation of smoking is important to endorse and encou rage even in the elderly. Finally, several periodic immunizations are advised in the elderl y, although their benefits for all subgroups is often debated. Pneumococcal vaccination is recommended at least once over the age of 65 yrs, with consideration of revaccination in ce rtain subgroups. Influenza vaccination is advised annu- ally for all elderly; although like ly the most effect approach to preventing influenza in nursing homes is to aggressively imm unize staff. Periodic (every 10 yrs) revaccination for tetanus is also advised. Vaccination to prevent shingles is now advised once in a lifetime >50 yrs. 652 This page intentionally left blank Biochemistry Paul E. Segal , D.O. and Joshua D. King , M.D. y r t s i Contents m e h c o B