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APPROACH TO DEMENTIA IN PRIMARY CARE HÜLYA AKAN, MD Assocc Prof of Family Medicine DEFINITION A syndrome, not a diagnosis An acquired degeneration of intellectual and cognitive abilities, which persists at least several months or takes chronically worsening course leading to major impairment in the patient’s everyday life Is not a normal process of aging PREVALENCE Prevalence doubles every 5 years after age 60. Over 85 years,it is about %25-45 The percentage of geriatric population is increasing all over the world. It shows that with increasing geriatric population, the number of dementia patients will increase It is the 6th leading cause of death in elderly population in the USA Approximately 2/3 of dementias are Alzheimer type dementia. Is it a community health problem? Geriatric population is increasing all over the world Only 10% of dementia is reversible, of these most of them to some extent Median life expectancy for AD patients 3-15 years Needs continous care at home and after than at an instituty As many as 90% of patients with dementia are eventually institutionalized. Median time to nursing-home placement is 3-6 yrs after diagnosis. (what about in Turkey?) What is Cognition? The operation of the mind by which we become aware of objects of thought or perception; it includes all aspects of perceiving,thinking and remembering Memory Orientation Language Judgement Perception Attention Ability to perform tasks in order What is normal cognitive change in elderly? Cognitive changes seen in normal aging - Age Associated Memory Impairement (AAMI) - Aging-Associated Cognitive Decline (AACD) Mild cognitive impairement (MCI) Dementia : usually complaint of relatives not the patient Cognitive changes seen in elderly Perform more slowly on timed tasks Slower reaction time Subjective problems such as difficulty recalling names or where an object placed The persons often remembers information later Intact learning Any deficits in memory function are subtle, stable and do not cause functional impairement Mild Cognitive Impairement Not within normal limits for the patient’s age and education but not severe enough to qualify as dementia Subjective memory complaint Objective memory impairement in the context of normal abilities on most other cognitive domains (language,executive function); and intact functional status May represent very early form of AD. Among patients with MCI; 10-15% per year convert to AD compared with 1-2% of age-matched controls They may progress to other types of dementias or remain stable-FOLLOW UP Dementia Most severe type of cognitive disorders Diagnosis requires multiple deficit in multiple domains of cognitive functioning Memory + At least one another that represent a significant change form baseline and that are severe enough to cause impairement in daily functioning Causes of Dementia Cerebral disorders without extrapyrimidal features Cerebral disorders with extrapyrimidal features Cancer Alzheimer disease Prominent memory loss, language impairement, visuospatial disturbance,depression,anxiety,delusions Pick disease Apathy,disinhibition,anosognosia,logorrhea,echolal ia,palilalia Creutzfeld-Jakob disease Myoclonus, ataxia,periodic EEG complexes Normal-pressure hydrocephalus Incontinence , gait disorder Dementia with Lewy bodies Fluctuating cognitive didorder, visual halucinations,parkinsonism Corticobasal ganglionic degeneration Parkinsonism, apraxia,cortical sensory loss,alienhand syndorome Huntington disase Chorea,pschosis Progressive supranuclear palsy Supranuclear opthalmaplegia,pseudobulbar palsy,axial distonia in extension Brain tumor Headache, focal neurologic signs,papiledema Meningeal neoplasia Focal weakness or sensory deficit,areflexia,pyrimidal signs,headache Infection Metabolic disorders Organ failure AIDS Oppurtunistic infections,memory loss,psychomotor retadation,ataxia,pyrimidal signs,white matter lesions on MRI Neurosyphilis Reactive CSF VDRL,pschosis,Argyll-robertson pupils,facial tremor,strokes, tabes dorsalis Progressive multifocal leukoencephaly Visual disturbances,white matter lesions on MRI Alcholism Prominent memory loss, nystagmus,gait ataxia Hypothyroidism Myxedema, hair loss,skin changes, hypothermia, headache, hearing loss, tinnitus, vertigo, ataxia, delayed relaxation of tendon reflexes Vitamin B12 deficiency Macrocytic anemia,low serum vit. B 12 level, psychosis, sensory disturbance, spastic paraparezis Dialysis demetia Dysarthria, myoclonus, seizures Non-Wilsonian hepatocerebral degeneration Cirhosis, eosaphageal ulcers, fluctuating mental satatus, dysarthria, pyrimidal and extrapyrimidal signs, ataxia Wilson disease Cirhosis, dysarthria, pyrimidal and extrapyrimidal signs, ataxia, decreased serum ceruloplasmin, Keiser-Fleischer rings of kornea Trauma Vascular disorders Peudode Headache, variable pyramidal and exrtapyramidal signs Chronic subdural hematoma Headache, hemiparezis,extraaxial collection on CT or MRI Vascular dementia Hypertension, diabetes, stepwise progression of deficits,hemiparezis,aphasia, infarcts on CT or MRI Depression Depressed mood, anhedonia,anorexia, weight loss, insomnia or Most Common Types of Dementia Alzheimer Disease 40-50% Mixed AD/Vascular dementia 15-20% Lewy Body dementia 10-20% Pick’s type (frontotemporal) 5-10% Vascular dementia 5-10% Other 5% Reversible Causes of Dementia Toxic affects of medications or drug interactions (especially elderly people use lots of drugs prescribed or unprescribed) Hydrocephalus-brain tumor Infection Electrolyte imbalance Malnutrition Endocrine and metabolic disorders Variable Dementia Delirium Depression Onset İnsidous/gradual Abrupt Fairly abrupt Duration Months-years Days-weeks Weeks-months Source of complaint Usually family, caregiver,friend Providers,family Patients themselves Level of conciousness/alertness Usually normal Varies throughout the day Usually normal Orientation Disoriented later in disease Usually disoriented early Usually normal Attention/concentration Good Poor Poor Effort Good Poor or fluctuating Poor “Don’t know” answers Uncommon Memory loss for recent vs. Remote information Greater for recent Greater for recent ~equal for both Lost of social skills Late Abrupt changes,labile Early Thought process/context Impoverished Disorganized May be slow Psychomotor symptoms Normal until late in the disease Hyper- or hypoactive Hypoactive ---- Common ALZHEIMER DISEASE Most common type of dementia DSM IV Diagnostic Criteria Developement of gradual cognitive deficits manifested both - impaired memory - aphasia, apraxia,agnosia, disturbed executive function Significantly impaired social, occupational function Gradual onset, continuing decline Not due to CNS or other physical conditions (e.g,parkinson, delirium) Not due to axis I disorder (eg. Schizophrenia) RISK FACTORS OF ALZHEIMER KNOWN Age Specific mutations on chromosomes 1,14,21 Family history Down syndrome Apolipoprotein E ε4 genotype PROBABLE Low education level Women Depression Brain trauma How Does Alzheimer Patient Apply to the Physician? Usually the complaint of family or caregivers not patient him/herself In early dementia patient usually apply to the physician for other reasons Patient aim to deny the illness – no in-sight Family members usually aim to relate the symptoms to other reasons- loss of partner, aging, recent operation etc How to Diagnose Alzheimer Disease Probable Diagnosis( usually clinical diagnosis) History Physical examination Cognitive tests DSM IV Criteria Definite Diagnosis - Brain biopsy COMMON COGNITIVE DISORDERS IN AD Memory Loss - Diffuculty in learning - Short term memory loss Disorientation - Time disorientation - Place confusion Aphasia -Anomia: naming of objects -Difficulty in finding words -Meaningless, undirected speech -Difficulty in understanding COMMON COGNITIVE DISORDERS IN AD Apraxia: -Ideamotor apraxia: Difficulty in turning an idea into movement (brushing teeth) -Extremity-kinetic apraxia:Difficulty in determining the place of own body parts in space (putting dress, sitting on chair) Complex Visual dysfunction - Agnosia: difficulty in recognizing - Visual spatial dysfunction COMMON COGNITIVE DISORDERS IN AD Disorder in applying -Disorder in planning -Disorder in judgement Disorder in abstract thinking Disorder in solving problem - Disinhibition Anosognozi - Unawareness of the disorder - Denial of the disease Common Noncognitive Signs in AD Personality Changes - Passive - Self-oriented - Agitated/irritable Apathy - Difficulty in beginning - Insufficiency to continue effort Depression Anxiety Common Non-cognitive Signs in AD Delusions - Paranoia - Misidentification Hallucinations Agitation - Nonspecific motor behaviours - Verbal agressiveness - Physical agressiveness Sleep disturbances - Circadian lapse - Insufficient sleep How to approach a patient presenting with cognitive problem First step : Is it a disturbance of level of conciousness (acute confusional state, coma) or content of conciousness (wakefullness preserved) Second step: Determine the cognitive function and the degree of cognitive impairement, decide dementia Third step: Differantiate reversible and irreversible dementia and also pseudodementia (e.g. depression) Check prescribed, unprescribed drugs and also herbal drugs and substance abuse (e.g,alcohol) Consider neurologic and neurophysciatric consultation Consider the treatment of reversible causes of dementia Consider treatment of dementia Consider daily activities scalas, determine the care needs of the patient Counselling of the patient, family and caregivers Consider treatment of behavioural disorders HISTORY TAKING Most important part of the diagnosis Altough it may be unreliable, first try to take the history from the patient. Asking questions about past and present social life and medical history gives lots of information about recent and remote memory. Don’t forget patient may feel uneasy with lots of questions and aim to deny self memory problem (no insight) Since patient has memory problem, you must confirm history by some one accompanying her/him. This also gives some clues about the degree of the problem. HISTORY TAKING Most of cognitive problems can be recognized and tested during history taking You may begin with asking “What do you like to do in your free times?” (Measure abstract thinking.For a meaningful response the patient must remember a list of activities and how they are organized). Alzheimer patients typically aim to answer with generalized terms (like reading). In this case clinician may specify by asking “What are you reading recently?” If patient has difficulty, the clinician must go into more detailed tests by saying “It seems you have difficulty in remembering some things. Maybe we better to do some more detailed tests.” HISTORY TAKING Special attention to drug use: Most of geriatric patients use lots of unprescribed and prescribed drugs having anticholinergic effects. Another problem is that the patient may forget and aim to take drugs several times a day.Ask for drug use and if possible ask for a written list and check with the patient and caregiver. Special attention to hearing and visional problems. These are also very common in elderly people. Undiagnosed problems may interfere with cognitive tests and may lead to lower scores. HISTORY Duration of symptoms and nature of progression of symptoms Presence of specific symptoms related to: -Memory (recent and remote) -Language (word finding problems, diffuculty expressing self) - Visuospatial skills (getting lost) - Executive functioning (calculations,planning, carrying out multistep tasks) - Apraxia (not able to do previously learned motor tasks eg:slicing of bread) - Behaviour or personality changes -Psychiatric symptoms (apathy,hallucinations,delusions,paranoia) HISTORY Functional assesment (ADLs, IADLs) Social support assesment Medical history, comorbidities Through medication review, including over-thecounter medications, herbal products Family history Review of systems including screening for depression and alcohol/substance abuse PHYSICAL EXAMINATION Cognitive examination General physical examination with special attention to: - Neurologic examination, looking for focal findings, extrapyrimidal signs, gait and balance assessment - Cardiovascular examination - Signs of abuse and neglect Screen for impairments in hearing and vision Cognitive Examination Rapid cognitive test MMSE Clock Draw Test Rapid Cognitive Test Most of the items can be performed during history taking and physical exam. Normal healthy adults usually finish this test in 5 minutes or less. It can show if there is need more detailed tests. Rapid Cognitive Test 1- Abstract Thinking: “What do you like to do in your free times?” A: If the answer is appropiate and well constructed or if there is no cognitive or behavioral signs, it may not needed further asssesment. B: If the answer is very concrete, suspicious or not including details, go on item 2. Rapid Cognitive Test 2-Focal Cortical function a: Learning:” I want you to repeat and keep in mind these three words, umbrella, rose, afraid” b: Memory/counting assessment: “If I give you one lira, five kuruş, ten kuruş and twenty five kuruş, how much money I would have given to you?” c: Naming:”Please tell me the name of the things I show you (shirt, jacket,pen etc)” Rapid Cognitive Test Temporaparietal tests 1- “Show how you nail on with your right hand” 2- Show how you use key when you are opening the lock with your left hand” 3- “Show how you slice a loaf of bread by using your both hands” 4-Touch your left ear with your right hand” 5- “Use your left hand to show my left hand” 6- “Before showing the ceil please show the door.” e: Drawings: 1- “Draw a clock and put the numbers in it and show the time 08:20.” 2- “Please draw the same of this figure” d: Rapid Cognitive Test f: Memory: “Please tell me the words that I have told you to memorize few minutes ago.” How to interprate? A: If the patient performs the tests in section 2, assess again in 6-12 months B: If patient can’t success in 2 or more parts of section 2 , consider more detailed assesment. Clock Draw Test Instructions “Draw the face of the clock, putting the numbers in the correct position. I’ll then ask you to indicate a time after you are done.” Ask the patient to draw in the hands at ten minutes after eight.” Scoring Draw a closed circle: 1 point Place numbers in correct position: 1 point Includes all 12 correct numbers: 1 point Correct indication of time: 1 point Clock Draw Test Interpration CTD 4: approximates MMSE nearly 30 or MCI CDT 2: puts the patient in moderate cognitive impairement, MMSE about high teens CTD 1 reflects moderate to low scores on mmse- low teens Clinical judgement MUST be applied Abnormal results needs further assesment MMSE Mini – Mental State Exam Not “ gold standart”, but most commonly accepted 30-point scale to evaluate orientation, concentration, verbal and visual spatial skills Subject to level of educational attainment, language barrier and vision/hearing requirements Scoring: Early stages: 21 - 30 Moderate stages: 11 - 20 Late stages: 0 - 10 LABORATORY CBC Electrolytes, Glucose, BUN/Cr.,Ca, LFTs Thyroid funtion tests Vit B12 VDRL (Syphilis),HIV (AIDS) ESR, Urine analysis Toxicology screen, 24 hour urine for heavy metals EEG (optional) Neuroimaging (optional) -CT: to rule out other dx -MRI: to rule out other dx PET, SPECT (optional) CSF fluids: High tau and low beta amyloid Is It Needed Neuroimaging? Routine brain imaging in the diagnostic evaluation of a patient with cognitive impairement dementia is controversial. If there is oppurtunity, uncontrasted CT or MRI is advised. New developments in diagnosis Functional imaging: FDG(fluorodeoxyglucose) PET- reduced use of glucose (sugar) in brain areas important in memory, learning and problem solving Molecular imaging technologies : highligts amiloid plaques in PET Pittsburgh compound B (PIB) 18F flutemetamol (flute) Florbetapir F 18 (18F-AV-45) Florbetaben (BAY 94-9172) How To Differentiate AD and Depression (Pseudodementia) Depression is common in dementia patients, also in elderlies. Clinically when they are found together it may be very diffucult to differentiate. In every patient you think dementia, try to differentiate pseudodementia- depression. Treatment of depression may improve cognitive problems. How To Differentiate AD and Depression (Pseudodementia) DEMENTIA DEPRESSION Insidious onset Abrupt onset Progressive deterioration Plateau of dysfunction No history of depression History of depression may exist Patient typically unaware of extent of deficits and does not complain memory loss Patient aware of and may exaggerate deficits and frequently complains memory loss Somatic complaints uncommon Somatic complaints and hypochondriasis common Variable affect Depressive affect Few vegetative symptoms Prominent vegetative symptoms Impairement often worse at night Impairement usually not worse at night Neurologic examination and laboratory Neurologic examination and laboratory studies may be abnormal studies normal When To Refer To Neurology Abrupt onset Extrapyrimidal symptoms or focal neurologic symptoms other than cognitive symptoms Abnormal neurologic examination except cognitive impairement Rapid deteriotion During follow-up new neurologic signs or symptoms unrelated to AD If you are not sure of the diagnosis When to Counsel for Neuropsychologic Tests? Neuropyschologic tests consist in-depth battery of standardized examinations that test multiple cognitive domains including intelligence,memory,language, visuospatial abilities,attention, reasoning and problem solving as well as other executive functions and applied by neurophysciatrists. Patients who have early or mild syptoms (diffuculty in diagnosing or differentiating) High premorbid intelligence Patients with low intelligence/educational level Is it needed Genetic Counselling? Late- onset AD (>60-65 yrs):Is associated with genes that increase the risk of AD but not in autosomal dominant fashion. ε4 increase AD 2-3 times, ε2 protective, but absence of ε4 does not rule out diagnosis. So it is not needed in practical means. Early-onset AD (<65 yrs, usually between 40-50 yrs): Familial.Inherited autosomal dominant. It is not needed in practical means, but if children of the patient wish to know whether they have inherited the gene, the family shoud be referred for genetic counselling. TREATMENT MAIN GOALS Preserve function and anatomy for as long as possible Maintain quality of life for both the patient and caregivers DRUG TREATMENT Cholinesterase Inhibitors: Effect sizes are modest in clinical trails 40-50% A stable or improved MMSE over 6-12 mo suggests the drug is effective. - Rivastigmine - Donezepil - Tacrine NMDA (N-methyl-D-Aspartate) Antagonists - Memantine Other pharmacologic agents tried have given controversial results Treatement of Behavioural Problems Commonly seen behavioural and psychiatric problems in AD: - Agitation and aggression - Disruptive vocalization - Psychotic features (delusions,hallucinations,paranoia) - Depressive symptom - Apathy - Sleep disturbances - Wandering or pacing - Resistance to personal care (bathing and grooming) - Incontinence Treatement of Behavioural Problems Antipsychotics (haloperidol,risperidone,olanzapine, trazadon) Antidepressants (SSRIs eg:sitoprolam) Mood stabilizers (eg: carbamazepine) Non-Pharmacological Treatement Music Reminiscence Therapy Exposure to pets Outdoor walks Bright light exposure Non-Pharmacological Treatement Advice to family and care givers: Maintain familarity and routines as much as possible Decrease number of choices Tell, don’t ask Understand they can’t, rather than they Won’t Don’t try logic or reason Always keep the goals in mind Follow-up Repeat MMSE every 6-12 months: In AD 3 point decrease/every year is expected Determine new behavioral changes and their causes Repeat complete physical examination including weight and determine if any new developed comorbidity Assess the efficacy of the drugs given for dementia (MMSE+ clinical judgement) Check medication list Check the stress level of caregiver SAFETY ISSUES Driving Home Safety: Every potential harms must be discussed detailly eg: stoves, carpets, lightining Wandering: sewn in clothing, identification bracelet Care giver assistance PROGNOSIS Median life expectancy 3-15 yrs Needs continous care Eventually becomes bed ridden In advanced dementia patient has difficulty with even most basic things such as feeding themselves Often urinary and bowel incontinence Patients who do not die of other comorbidities tend to develope concomitant complications (malnutrition, pressure ulcers,recurrent infections) The most common cause of death is pneumonia. EVIDENCE BASED POINTS AD is the most common form of dementia, accounting approximately 66% of patients with dementia Routine brain imaging in the diagnostic evaluation of a patient with cognitive impairement dementia is controversial. Genetic testing, including APOE genotyping,is not indicated for clinical use. Actylcholinesterase inhibitors for tratement of AD have modest benefits on cognition, physical functioning and behaviour. Behavioral and psychologic symptoms of dementia are associated poor outcomes.