3. Dementia and Behavioral Neurology Flashcards
A 78 year-old woman started forgetting conversations and appointments 6 years ago. Her memory loss progressively worsened over that time. Though she remains pleasant and friendly, at times she feels people have been stealing money from her purse. She can no longer recognize her own grandchildren, and recently, she has been wandering away from the house and getting lost. Other than her MMSE, where she scores 20/30, a neurological exam is normal. What is the most likely diagnosis for this patient?
Alzheimer’s disease
Pathogenesis
- Atrophy of the mesial temporal lobe (hippocampus)
- Primary motor and visual cortices are preserved
- Over time, there is diffuse brain atrophy
What is the difference between dementia and mild cognitive impairment?
Dementia = impairment in 2/5 functional domains that impact ADLs:
- Memory
- Emotion
- Executive function
- Language
- Visuospatial
Mild cognitive impairment = cognitive impairment that does not meet criteria for dementia
- Risk factor for developing Alzheimer’s disease
What are the different types of memory?
Episodic memory
- Memory of personal experiences
- Primarily affected in Alzheimer’s disease
Semantic memory
- Memory of facts
Declarative memory
- Semantic memory + episodic memory
Procedural memory
- Memory of how to do things
- Less affected in Alzheimer’s disease
A 78 year-old woman started forgetting conversations and appointments 6 months ago. Though her symptoms are quite mild, you strongly suspect that she is in the early stages of Alzheimer’s disease. After completing a full diagnostic work-up, you suggest starting treatment with…
Cholinesterase inhibitors
- Galantamine, tacrine, donepezil, rivastigmine
- There is improvement in cognitive function and psychiatric symptoms
- They do NOT delay natural history of Alzheimer’s disease
Acetylcholine is produced in the nucleus basalis of Meynert
Alzheimer’s disease is characterized by neurofibrillary tangles and amyloid plaques in the cerebral neocortex and hippocampus.
Several medicines are used to treat the symptoms of Alzheimer’s disease. Donepezil (Aricept) is in a class of medicine known as acetylcholinesterase inhibitors. Another medicine used to treat Alzheimer’s disease is memantine (Namenda). It has been shown to improve patients’ functional abilities and relieve caregiver burden. Its mechanism of action is to decrease glutaminerigic overstimulation by which mechanism?
NMDA (glutamate) receptor antagonist
- Glutamate = major stimulatory NT in CNS
- GABA = major inhibitory NT in CNS
Alzheimer’s disease is uncommon in patients less than 60 years old. In such patients, where the disease often runs in the family, what protein is likely to be mutated?
Amyloid precursor
- Amyloid-beta precursor protein (ABPP) mutations may cause increased amyloid-beta production with subsequent aggregation in the neurons
Which of the following abnormalities is most likely to be associated with the underlying disease process in Alzheimer’s disease?
Presence of the e4 allele of apolipoprotein E (ApoE4)
- ApoE has a central role in cholesterol transport
- In families with late-onset AD and ApoE4 allele,
- Risk increases from 20% to 90%
- Mean age of onset decreases from 84 to 68 years
In which genetic disease is Alzheimer’s disease an inevitability?
Down’s syndrome
All of the following are true regarding Alzheimer’s disease EXCEPT:
- Age is the most important risk factor
- Women are affected at a higher rate then men
- A diagnosis of the illness can be made based on characteristic findings on the MRI even in the absence of significant cognitive impairment.
- A high education level is protective against developing the illness
- It is the most common cause of dementia in patients over age 65
A diagnosis of the illness can be made based on characteristic findings on the MRI even in the absence of significant cognitive impairment.
How can delirium be best distinguished from Alzheimer’s dementia?
Fluctuations in level of arousal
An 87 year-old man with dementia is admitted from a nursing home for agitation and confusion significantly greater than his baseline. He is agitated, combative, and does not know where he is. What is the most appropriate next action?
Urinalysis to detect a possible UTI
Evaluation of a patient with dementia involves:
- Electrolyte panelrenal function, hepatic function, TSH, syphilis test, B12, UA, tox screen, HIV test
- Neuroimaging
- List of medications - look for anticholinergic medications, benzos, opiates
- Depression screen for “pseudodementia”
- LP and EEG if there are “red flags”:
- Early onset or rapidly progressing dementia
- Immunocompromised patient
- Focal neurological findings
- Signs of systemic illness
- Dementia is distinguished from delirium by its lack of a waxing and waning course
A 72 year-old woman with dementia is paranoid and has visual hallucinations. The patient’s family says that her symptoms fluctuate throughout the day. She is started on Risperdal 0.25mg for periods of agitation, and two days later is more confused with new onset rigidity. What is the most likely diagnosis?
Diffuse Lewy body disease (DLBD)
Lewy bodies are composed of alpha-synuclein and are seen in other neurological disorders (namely Parkinson’s disease)
Central feature of DLBD is progressive cognitive decline combined with:
- Severe fluctuations in alertness and attention
- Prominent visual hallcuinations
-
Parkinsonism (rigidity, bradykinesia, shuffling gait)
- Patients are hypersensitive to antipsychotics
- Treatment of neuropsychiatric disorders can worsen parkinsonism; treatment of parkinsonism can worsen neuropsychiatric disorders
- Sleep disturbance
- Orthostatic hypotension
A 66 year old man is brought to your clinic for slowly progressive symptoms of dementia. Which of the following symptoms would help you distinguish between diffuse Lewy body dementia and Parkinson’s disease?
Fluctuating cognition
- Fluctuating cognition with variations in attention and alertness is highly suggestive of DLBD
- Both DLBD and PD may present with parkinsonism (bradykinesia, rigidity, gait abnormalities) and deficits in executive function
An 87 year-old man with cataracts reported seeing people and animals in his house—including bears and small cattle. He knew that these visions were not real and they didn’t bother him much, but he thought he might be losing his mind. What is the most likely diagnosis?
Charles Bonnet syndrome
- Patients are mentally healthy, often with significant visual loss
- Typical hallucinations include small animals and people
- Patients understant the hallucinations are not real and they are typically not bothered by them
A 59 year-old man starts yelling at his wife and children for even minor offenses. Previously, he had been a calm person. Additionally, he starts paying poor attention to his grooming, showering infrequently and wearing the same clothes several days in a row. He is brought to medical attention after he was arrested for soliciting a prostitute. A neurological exam, including basic memory testing, is normal, as are basic labs and a urine toxicology screen. What is the most likely diagnosis?
Frontotemporal dementia (FTD)
- Significant alterations in personality, social behavior, and language
-
Unlike AD, FTD presents initially with cognitive and behavioral deficits other than memory loss
- Neglect social and personal responsibilities
- Failure in judgment
- Occurs at a younger age (< 65) and has more rapid progression than other dementias
- Memory is often unaffected
- Abnormal tau protein - tau-positive inclusions found in neurons and glial cells
- Pick disease is a rare form of FTD characterized by personality change, speech disturbance, inattentiveness, extrapyramidal symptoms
A 56 year-old woman slowly loses interest in all of her daily activities. Formerly she was a high functioning mathematician who enjoyed giving tours of New York City historical sites. Her husband says she sits in a chair all day and does nothing. She was treated with standard medications for depression which were ineffective and eventually given a trial of ECT, which made her very confused. On exam, she is disheveled and sits passively in the chair. She answers all your questions, but does not engage with you in a meaningful way. MMSE is 30/30 and the rest of the exam is WNL. What is the most likely diagnosis?
Frontotemporal dementia (FTD)
Damage to frontal lobes can produce 2 different patterns of behavior:
-
Apathy, abulia (inability to act decisively), mutism
- Neglect of personal hygience, repetitive or compulsive behavior, decreased energy and motivation
- Primary progressive aphasia = global language difficulties
-
DIsinhibition, poor judgment, antisocial behavior
- Inappropriate social behavior, lack of social tact, lack of empathy, distractability, loss of insight into the behaviors of oneself and others, an increased interest in sex, changes in food preferences, agitation
A 54 year old woman who has been your patient for years comes in for a follow-up visit. Her mood is noticeably low and she reports feeling very down. When pressed she admits to significant financial troubles due to increased time spent gambling at a nearby casino and purchasing many scratch-off lottery tickets on a daily basis. She maintains that she has never been that interested in casinos in the past, but now finds herself there almost every weekend. What medication is this patient most likely taking?
Ropinirole (Requip)
- A dopamine agonist used to treat PD
- Side effect includes increased impulsivity (gambling or hypersexual behavior)
- A 56 year-old man has exhibited memory problems for 1 month, and he is noted by his immediate family to tell elaborate stories that are interesting, though entirely false. He has a long history of alcohol dependence. On exam, he is ataxic while walking and has nystagmus. What is the most likely diagnosis?
- What area of the brain is typically damaged?
- Wernicke-Korsakoff syndrome
- Mamillary bodies
- Caused by deficiency in thiamin (vitamin B1)
- Rapid clinical onset
- Typically in chronic alcoholic patient who receives IV glucose
- Core feature = confabulations
- Unintentional creation of false memories or beliefs
- Symptoms:
- Ataxia of gait
- Encephalopathy
- Eye movement disorders - nystagmus, opthalmoparesis (paralysis maily with lateral gaze)
- Amnesia
A 37 year-old man, seen below, tells you that he is in fact 39 years old. He tells you that he is in the hospital, but gives the name of the hospital up the street. He says the president is Bush and tells you the wrong date by 1 month and 1 year. The term for this pattern of answering questions is called…
Ganser’s syndrome
- Also called prison psychosis
- An atempt to manipulate legal situation = malingering
A 77 year-old man has become demented over the course of 7 years. His condition is marked by years of stability followed by abrupt declines in his cognitive ability. On physical examination he is weak on the entire left side of his body, and has a subtle receptive aphasia. Neuroimaging is pending. Which of the following is the most likely diagnosis?
Vascular dementia
- Presents in “step-wise” fashion and in patients with focal neurological deficits
- Risk factors = age, HTN, DM, HLD, smoking
- Lesions include hippocampus, medial thalamus, caudate nucleus
A 67 year-old man presents with a 1-year history of cognitive deficits manifest primarily by difficulties with sustaining attention and short-term memory problems. Prior to this, he was well, though he did have bacterial meningitis 5 years prior from which he recovered. On exam, his feet seem glued to the floor when he walks, and he is also noted to smell of urine. The remainder of the exam is normal. What is the most likely diagnosis?
Normal pressure hydrocephalus (NPH)
- Triad = magnetic gait, dementia, urinary urgency/frequency
- “Wobbly, weird, wet”
- Dx = continuous lumbar drain
- Tx = VP shunt
- Risk = subdural hematoma
- Indications
- Presence of clear etiology of hydrocephalus
- Gait difficulties > cognitive impairment
- Substantial improvement after removal of CSF
- Lack of atrophy and white matter lesions
- Etiology
- Previous subarachnoid space pathology (meningitis, subarachnoid blood) that interferes with reabsorption of CSF in arachnoid granulations
A patient undergoes a ventriculoperitoneal shunt placement for hydrocephalus. Two days later, he is confused and complains of headache. Although he was walking the previous day, he is unable to walk when examined today. What is the most likely cause for these symptoms?
Subdural hematoma
- Patients who have undergone a VP shunt placement are at risk for developing subdural hematomas due to reduction of ICP that pulls in the brain away from the meninges and tears veins
A 62 year-old female presents with new onset psychosis and memory loss. While in the ER, she has a seizure. An MRI reveals hyperintensity of the mesial temporal lobe structures and frontal lobes bilaterally. A CSF analysis shows anti-Hu antibodies. Her presentation is most consistent with…
Limbic encephalitis
- A paraneoplastic syndrome caused by autoantibodies and associated with cancer
- Types:
- Anti-Hu Abs = small cell carcinoma of lung
- Anti-Ma2 = germ cell tumors of testis
- Anti-NMDAR = ovarian tumor (usually teratoma)
A 58 year old man is brought into his primary care physician’s office by his very concerned and flustered daughter. She says that he has become a completely different person in the last three months. Today, she went to his home, where he lives by himself and noticed the house in complete disarray. He was lying on the couch, looked as though he had not moved or showered in a week, and bills and trash were piling up. She also noticed that he had a lot of messages on his machine from his colleagues stating that they were concerned because he had not been going to work recently. As she was struggling to leave to take him to the doctor, a car backfired and he started shaking and jerking seemingly uncontrollably for a short period of time.
- What is the diagnosis?
- What is the prognosis given the biopsy results below?
- Creutzfeldt-Jacob Disease (CJD)
- Death with or without intervention
- A prion disease characterized by rapid onset change in mental status + myoclonus
- Accumulation of prion protein in the brain leading to neuronal loss, gliosis, astrocyte proliferation
- Symptoms:
- Dementia, behavioral abnormalities, deficits in concentration and memory, apathy, depression
- Myoclonus, hypokinesia, nystagmus, ataxia
- Dx = presence of protein 14-3-3 on brain biopsy
- Tx = none, death within a year
Henry Gustav Molaison, known for decades only as HM, died in 12/2008. He was famous for being utterly unable to form new, conscious memories after having surgery for epilepsy where lesions were made to…
Bilateral hippocampi
The hippocampus is necessary for encoding memories
- It is atrophied in Alzheimer’s disease, epilepsy, medial temporal lobe sclerosis
A 45 year-old woman presented to the emergency room with her family. They said she has been making unwelcome sexual advances to strangers, has been putting objects in her mouth, is suddenly unafraid of things that used to terrify her, and is “not her feisty self.” Her MRI is shown below.
- What is her diagnosis?
- Where is the damage located?
- Kluver-Bucy syndrome
- Bilateral amygdalae
Characteristics:
- Hypersexuality
- Placidity - diminished fear response and docile in settings that should normally trigger fear, aggressiveness, or anger
- Hyperphagia and hyperorality - patients overeat, put things in their mouth, eat inedible objects
- Visual agnosia - difiiculty recognizing familiar faces or objects
A patient has the sudden onset of language difficulties. He is able to say phrases and sentences with correct grammar, but his speech is essentially nonsensical. He is unable to repeat phrases or follow complex commands. He seems blissfully unaware of any problem.
- What is the name of this type of aphasia?
- Where is the lesion?
- Wernicke’s (receptive) aphasia
- Left superior temporal gyrus
Wernicke’s aphasia is the inability to understand language or repeat phrases
- Intact speech production
- Speech is nonsensical
- Patients are NOT aware of the deficit
- Usually NOT associated with weakness
Transcortical sensory aphasia
- Wernicke’s but with intact repitition
A patient has the sudden onset of language difficulties. He understands what is said to him but can only say short, 2-3 word phrases with great effort, and he cannot repeat phrases said to him. He is clearly frustrated by this problem and swears effortlessly out of frustration.
- What is the name of this type of aphasia?
- Where is the lesion?
- Broca’s (expressive) aphasia
- Left inferior frontal gyrus
Broca’s aphasia is inability to produce language or repeat phrases
- Intact comprehension
- Patients are aware of their deficit
- Often have profound right sided weakness
Transcortical motor aphasia
- Broca’s but with intact repitition
A patient has the sudden onset of language difficulties. On exam, he has mild word-finding problems, significant trouble naming objects, and a marked inability to repeat phrases. He is able to follow simple commands.
- What is the name of this type of aphasia
- Where is the lesion?
- Conduction aphasia
- Arcuate fasciculus
Conduction aphasia is characterized by:
- Intact auditory comprehension
- Fluent speech production, but poor speech repetition.
- They are fully capable of understanding what they are hearing, but show significant difficulty repeating phrases and stumble over words they are attempting to pronounce
A patient has the sudden onset of language difficulties. His speech is fluent, his comprehension is intact, and he can repeat phrases. However, his speech is flat and monotone, without the proper intonation that characterizes normal speech. His family says that this is a significant change from the patient’s baseline.
- This patient’s symptom is classified as…
- Where is the lesion?
- Abnormal prosody
- Right inferior frontal gyrus
A patient suddenly believes his wife is speaking a foreign language to him. It turns out that he can understand no one who is talking to him. Yet, he can read, write, and speak perfectly well. He can also hear, as evidenced by his ability to recognize sounds and music.
- What is the name of this aphasia?
- Where is the lesion?
- Pure word deafness
- Bilateral primary auditory cortex
- Pure word deafness is caused by bilateral damage to the posterior superior temporal lobes or disruption of connections between these areas
- Characterized by inability to comprehend the meaning of speech
- Still able to hear, speak, read, and write
A patient is brought in by his family for the sudden inability to speak. After observing the patient for several days, you determine he CAN speak, but only chooses to do so under extreme duress. You localize the lesion to the…
Bilateral cingulate gyri
- Cingulate gyrus is a fold in the brain superior to the corpus callosum involved with emotions and regulation of aggresive behavior
- Abnormalities have been implicated in psychiatric diseases such as schizophrenia and OCD
- Language pattern is called akinetic mutism
A 64 year-old man has a tumor which causes him to have the following findings on neurological exam: right/left confusion and difficulty subtracting serial 7’s.
- What is the diagnosis?
- Where is the tumor?
- What other findings might he have on examination?
- Gerstmann’s syndrome
- Dominant parietal lobe
- Agraphia
Gerstmann’s syndrome is caused by a lesion to the dominant angular gyrus - a region of the parietal lobe near the superior edge of the temporal lobe
Agraphia = deficiency in ability to write
Acalculia = difficulty in learning or comprehending mathematics
When asked to draw the face of a clock, a 67 year-old stroke victim produces the following image. Additionally, though she is quite weak on the left side of her body, she denies there is any problem at all. The patient most likely has a lesion in what part of the brain?
Right parietal lobe
A 45 year-old woman lost the ability to recognize the face of her own good friends. This deficit is called prosopagnosia and localizes to the…
Fusiform gyrus of the temporal lobe
A patient cannot recognize a coin or paper clip placed in her right hand when her eyes are closed but she has no trouble with her left hand.
- What is this called?
- Where is the lesion?
- Astereoagnosia
- Parietal lobe/primary somatosensory cortex
A patient is referred to a psychiatrist for “hysteria.” She says that she woke up last week unable to read. When examined by the referring physician, the patient could write, but unbelievably could not read back what she had just written. She otherwise has a normal mental status examination, though you think you detect a right homonymous hemianopsia. Where is the lesion?
Left occipital lobe, involving the splenium of the corpus callosum
- The patient has alexia (inability to read) without agraphia (inability to write)
- Visual information reaches only the right occipital lobe, but cannot be accessed by the language areas of the brain (left parietal lobe) and therefore the patient cannot read
- Since language areas are otherwise fine, the patient can write
A 36 year-old male develops the acute onset of confusion and cortical blindness. His MRIs are below.
- What is the diagnosis?
- What is this usually due to?
- Posterior reversible encephalopathy syndrome (PRES)
- Sudden, drastic increase in blood pressure
- Commonly seen as a consequence of severe uncontrolled hypertension
- In women, commonly caused by eclampsia
- Most common in occipital lobes but can occur in posterior circulation (cerebellum)
- Clincal presentation:
- Seizures
- Visual disturbances
- Headache
- Mental status changes
A patient is referred to you by his family doctor because he keeps insisting that “numbers have colors.” When you ask him to show you what he means, he produces the following drawing. A thorough neurological work-up was normal. What is the term for this condition?
Synesthesia
A 67 year-old woman is referred to a psychiatrist for “hysteria” after she reports being unable to use utensils to eat her food. She says that her left arm “has a mind of its own” and at times, tries to undo actions she has just performed. The term for this is…
Alien hand syndrome
- Can result from several different types of diseases
- When associated with dementia, occurs in corticobasal degeneration
- Can occur after epilepsy surgery where the corpus callosum is severed to prevent generalization of seizures
