Dementia: A brief overview to approach and management
Great internal website: http://www.med.umich.edu/i/neuro/cd/index.htm
Dementia definition:
Cognitive or behavioral symptoms that:
• Interfere with ability to function at work or at usual activities
• Represent decline from a previous level of functioning
• Are not explained by delirium or psychiatric disorder
• Are diagnosed by history and examination
• Involve at least 2 cognitive domains, such as :
- Memory
- Reasoning and judgment
- Visuospatial
- Language
- Personality, behavior, comportment
Clinic dementia evaluation/management:
1) Taking a cognitive disorders history: It is KEY to get accounts of both patient AND a reliable
witness who knows the patient; often the patient will not think there is a problem, while witnesses/family will
be the ones concerned.
-Memory/executive function: Specific examples? Forget conversations, misplacing things, keeping
calendars/lists, missing exits when driving, getting lost in familiar places, not able to deal with detours/follow
written directions, forget birthdays/names, miss appointments, not able to manage own meds/bills correctly.
Keep track of current events. Understanding TV show/movie, shopping. Long-term memory problems. Are the
problems any different from other friends the patient’s age?
-Language: Understanding what others are saying, word-finding, naming, having people need to repeat things,
reading/writing.
-Judgment: Would they be trusted to make major financial decisions?
-Personality changes: Disinhibition, impulsiveness, irritability, decreased verbal output, apathy/sedentary
behavior, hypersexuality, OCD, excessive spending, changing dietary habits/overstuffing mouth, hygiene.
-Psych: Hallucinations/delusions/paranoia, fluctuations in attention, depression (SIGECAPS).
-Is cognitive problem impacting daily functioning (MCI vs. dementia): ADLs/IADLs, what patient likes to do (and
has that changed), limitations, ?employed, whether spouse would feel comfortable leaving them alone at
home for 1 week.
-Danger signs : Wandering out of house at night, leaving stove on, violent/destructive behavior, dangerous
driving, etc
-Misc: OSA screening, h/o head trauma, h/o parkinsonism, ? polypharmacy/med list, substance use, head injury,
stroke/TIA or focal neurological symptoms, seizures or altered mental status, falls, incontinence, dysphagia, sleep habits,
gait or movement difficulties, family Hx, education level.
2) Exam:
-Usually best to start with MOCA, as more sensitive for more subtle changes. For following cognitive status
over time if already impaired, serial MMSE’s are sufficient.
-If language concerns, have them name objects (can give choices if can’t name them), point to named objects
in the room, detailed repetition, read/write things.
-Geriatric depression screen
-Full neuro exam; Parkinsonism?
3) Testing:
-Note: “Definite” diagnosis of dementia is only possible with autopsy; clinical diagnosis is “probable” or
“possible”.
A) Labs (reversible causes of dementia): CMP, B12/MMA, TSH/T4. Additional labs only if clinical suspicion for
very atypical/specific presentations.
B) Imaging: Some baseline head imaging (MRI is preferable to non-contrast CT), looking for atrophy,
significant vascular disease, or other secondary causes (bleed, tumor, etc); PET scan only if question is
SPECIFICALLY “AD vs. FTD” (otherwise, insurance won’t pay for it).
MRI/CT:
-AD: Classically diffuse atrophy that is possibly more notable in temporal and parietal regions. Tends to spare
occipital lobe.
-Vascular: Extensive WM disease or large/ very numerous infarcts. Not SPECIFIC for vascular dementia.
-FTD: Atrophy of anterior temporal and frontal regions.
PET:
-AD: Hypometabolism classically temporal, parietal, and posterior cingulate gyrus (ie, posterior predominant);
as disease progresses, can involve whole brain. Dominant hemisphere hypometabolism often associated with
language variant, nondominant hemisphere is visuospatial variant.
-FTD: Hypometabolism in anterior temporal, frontal, and anterior cingulate regions.
-LBD: Hypometabolism prominent in occipital region, but can also have a lesser element of AD pattern
(temporal, parietal, posterior cingulate)
-PSP: Hypometabolism in subcortical structures
C) Neuropsychiatric testing: Helpful for diagnosis, and also for baseline in case serial monitoring needed.
Buzzwords to look for on testing:
-AD: Memory predominant
-FTD: Language executive dysfunction
-Vascular: Attentional and executive dysfunction, focal deficits, multidomain, subcortical.
-LBD: Visuospatial.
D) If special concerns: ? PSG, ? EEG, ? LP, etc.
4) Management of Dementia:
AAN practice parameter: http://www.neurology.org/content/56/9/1154.short
A) Basics:
-Goal is as much independence as SAFETLY possible.
-Have someone observe patient managing meds, driving, and doing finances, and if concerns then patient may
need assistance with them.
-If significant cognitive impairment or family concern for driving safety, get OT driving safety eval and DO NOT
drive until it is obtained and passed.
-Get DPOA established (social work can assist with this process).
-Is living situations adequate/does patient have adequate supervision (if not, consider home health aides vs.
assisted living)?
-Weight loss? Adequate nutrition? Dysphagia? Good sleep?
-No need for specific diet or activity (besides healthy diet, exercise, and staying mentally active and engaged).
-Correct other contributors (depression, OSA, polypharmacy, etc)
-Identification programs for patients that are prone to wandering.
-Social activities/support activities/support groups
-Patient/family safe? (agitation, dangerous behavior, etc)
-Interested in research?
B) Pharmacologic therapies:
-Donepezil (Aricept):
-Cholinesterase inhibitor. 5mg QHS for awhile, and if tolerated then go up to 10mg QHS.
-Side effects: Somnolence, diarrhea/GI upset, bradycardia. No drug-drug interactions.
-“Stops the clock” for 6 months, but doesn’t reverse decline and doesn’t slow/stop decline forever
-Caution in patients with cardiac disease, heart rhythm issues/bradycardia, or COPD/asthma.
-FDA approved for: AD
-Commonly used for: AD, PDD, LBD
-Galantamine
-Cholinesterase inhibitor.
-4mg BID for awhile, then increase slowly to maximum of 12mg BID
-Side effects: Somnolence, diarrhea/GI upset, bradycardia.
-Rivastigmine (Exelon oral or patch)
-Cholinesterase inhibitor.
-Begin 1.5mg BID. Increase gradually up to 13.3 mg/day
-Side effects: Somnolence, diarrhea/GI upset, bradycardia. Patch usually MUCH better tolerated.
-FDA approved for: AD, PDD (oral form only)
-Commonly used for: AD, LBD, PDD.
-Memantine (Namenda):
-NMDA receptor antagonist. Increase slowly to 10mg BID; comes with titration pack to aid in this.
-Only beneficial in moderate-to-severe (NOT mild) AD and LBD. Rule of thumb: prescribe if MMSE
<15/30
-Use caution in patients with seizures (theoretical risk) and renal disease (if CrCl <50, renally adjust to
5mg BID).
-No significant side effects.
-FDA approved for: Severe AD
-Commonly used in: Severe AD
-Agitation: Consider low-dose Seroquel, referral to gero-psych. Avoid Ativan or Xanax as can cause paradoxical
worsening.
Information on specific dementias
Characteristics of particular dementias (generally):
-Alpha-synuclein/Lewy Body diseases: PD, LBD, MSA, Alzheimer’s. Frequently associated with REM sleep
behavior disorder (RBD) and anosmia (exception: AD almost NEVER has RBD).
Vs.
-Tau-opathies: FTD, CBD, PSP
MCI:
-Cognitive impairment, but can still function independently in normal day-to-day things (work, social,
ADLs/IADLs) without limitation.
-Amnestic vs. multidomain vs. single (non-amnestic) domain.
-12-15% cumulative risk per year of converting to dementia (after 2 years 30% risk, after 3 years 45% risk, etc),
though there are cases of possible reversal or prolonged stabilization of MCI.
AD:
1) Epidemiology/pathophysiology:
-Major risks for disease: Age, family hx (only 5% can be tied to specific genes), and cardiovascular disease.
-Pravelence is 1% at 60 years, and doubles every 5 years after that.
-Cause is unknown, but neuron death is primary problem. Classic pathology is amyloid plaques and
neurofibrillary tangles.
2) Signs/symptoms:
-Commonly present with memory >> language and praxis issues, though affects multiple domains.
-Memory problems usually are short term (learning new things); once it becomes severe, long term memory is
also affected.
-Language problems usually are word-finding problems; retained fluency and repetition.
-30-50% of patients with memory problems will not even agree that they have memory problems, even in
early stages of the disease.
-Later in disease, also commonly see depression (36%), seizures (10-20%), weight loss (40%), cirdadian rhythm
disturbances (25%), and hallucinations (10-20%).
3) Diagnosis:
-AD diagnostic criteria: http://www.alzheimersanddementia.com/article/S1552-5260(11)00101-4/pdf
-Probable AD: Dementia + insidious onset + the most prominent early feature is one of the following:
Amnestic + one other cognitive domain; language (word finding); visuospatial (facial recognition,
simultagnosia, alexia); executive dysfunction (judgment, reasoning, problem solving).
-Possible AD: Above criteria, but with either atypical course or mixed presentation.
4) Prevention:
No intervention currently reduces risk, though generally recommend healthy diet, exercise, mental
stimulation, and minimize cardiovascular risk factors.
5) Prognosis:
-Mean time from diagnosis to death is 6 years.
NOTE on Logopenic progressive aphasia:
- PPA variant of AD, NOT FTD. Resembles nonfluent variant PPA.
-Presents with TROUBLE RETRIEVING WORDS: slow speech, paucity of speech/mutism, impaired naming,
impaired repetition. Retained understanding of the MEANING of words.
-Tend to perform poorly in memory and calculations tests.
-Atrophy in dominant posterior temporal lobe and parietal lobe (more characteristic of AD than FTD)
Vascular:
-Tends to be more attention/executive/frontal dysfunction; can also see focal cognitive deficits
-Classically step-wise cognitive decline, due to deficits from repeated infarcts.
-Just because someone has a little white matter disease and vascular risk factors, doesn’t mean it is
necessarily vascular dementia (despite what the neuropsych testing report says).
-Focus on modifying vascular risk factors
LBD:
1) Signs/symptoms:
-Dementia starting before or around the same time (ie, within a year or so) as parkinsonism.
Classically with early formed visual hallucinations (usually people/children) and fluctuations in
attention.
-50% have RBD; almost no patients with AD have RBD.
-Fluctuations in attention may be mistaken for seizures, symptoms of OSA, result of poor sleep, or
medication effects/delerium.
-It is likely that PD and LBD are the same alpha- synuclein disease, just on a spectrum: with PD the
pathology starts subcortically and spreads cortically (thus early parkinsonism with late dementia),
while LBD the pathology starts cortically and spreads subcortically (early dementia with later
parkinsonism).
2) Diagnostic criteria:
-Probable LBD: Progressive cognitive decline + 2 of the following MAJOR criteria: fluctuating
attention/alertness, visual hallucinations, motor parkinsonism.
OR
Progressive cognitive decline + 1 of the MAJOR criteria + one of the following MINOR criteria: REM
sleep behavior disorder, severe neuroleptic sensitivity, or suggestive PET scan.
3) Tx:
-Cognitive: Aricept significant improvements lasting at least 12 weeks and reducing caregiver burden.
Anecdotally, it can be quite helpful.
-Avoid antipsychotics and sedative-hypnotics if possible; if needed, prefer quetiapine or clozapine as
less likely to worsen parkinsonism or cause paradoxical confusion. LBD patients are often “more
sensitive” to medication side effects.
-Parkinsonism: Sinemet can often be effective, but need to balance with risk of worsening cognitive
symptoms. Avoid dopamine agonists due to high risk of side effects in this population.
4) Prognosis:
-Average survival from time of diagnosis is 8 years.
FTD:
1) Pathophysiology/epidemiology:
-Onset between age 35-75 (usually younger than AD patients); equal M/F ratio
-20-40% will have family history
-Primary due to selective loss of spindle neurons
2) Signs/symptoms:
-Usually presents primarily with either EARLY 1) Behavioral or 2) language problems. Memory is usually mostly
preserved until later in disease.
-Often can be associated with ALS (FTLD-TDP43)
A) Behavioral variant:
-Disinhibition (inappropriate behavior, impulsivity, hypersexuality), apathy, poor judgement, OCD behavior,
poor hygiene/diet/overeating, indifference to condition. Generally REMAIN ORIENTED without true amnestic
components.
B) Language (primary progressive aphasia) variant:
i) Nonfluent/agrammatic variant PPA: Trouble with finding the correct word for something, trouble
reading/writing. PRESERVED UNDERSTANDING OF WORD MEANING. Become mute. Basically progressive
nonfluent aphasia, can still understand words/sentence, retained word meaning.
ii) Semantic variant PPA: Can’t name things, CAN’T UNDERSTAND WORD MEANING. Basically NOT
UNDERSTAND words/meaning.
3) Diagnosis:
-FTD Diagnostic criteria: http://memory.ucsf.edu/ftd/medical/diagnosis/criteria/single
A) Behavior variant, possible: At least three of the following: Behavior disinhibition, apathy, lack of
sympathy/apathy, OCD, hyperorality/dietary changes, executive dysfunction with sparing of memory and
visuospatial.
-Behavior variant, probable: Possible criteria, plus functional decline, plus suggestive imaging findings.
B) Semantic variant PPA:
-PPA (aphasia is most prominent component of symptoms + impairing daily living) + difficulty with language
(word-finding deficits, paraphasias, effortful speech, grammatical and/or comprehension deficits)
AND
-Lack of prominent early behavior or memory disturbance
AND
-Poor naming of pictures/object + impaired single word comprehension + 3 of the following: Poor object
knowledge, Surface dyslexia and/or dysgraphia, Spared repetition, Spared motor speech/grammar
AND
-MRI with anterior temporal atrophy or PET with anterior temporal hypometabolism
C) Nonfluent variant PPA:
-PPA (aphasia is most prominent component of symptoms + impairing daily living) + difficulty with language
(word-finding deficits, paraphasias, effortful speech, grammatical and/or comprehension deficits)
AND
-Lack of prominent early behavior or memory disturbance
AND
-Either agrammatism or Effortful/halting speech
AND
-At least 2 of the following: Impaired comprehension of syntactically complex sentences, Spared single word comprehension,
Spared object knowledge
AND
-MRI with left posterior fronto-insular atrophy or PET with left posterior fronto-insular hypometabolism
Rapidly progressive dementia workup:
-Usually warrants hospital admission to expedite workup.
-DDx: Includes paraneoplastic/neoplastic, neurodegenerative (CJD or fulminant forms of LBD, PSP, CBD, FTD,
AD, NPH), epileptic, autoimmune/inflammatory (including vasculitis), toxic/metabolic (including meds),
psychiatric (severe depression, catatonia, etc), infectious, ischemic (strokes/vascular dementia, CADASIL), misc
(mitochondrial).
-Exam: Make sure to document degree of impairment (MMSE if possible), any parkinsonism, startle myoclonus
or other abnormal movements.
-Labs: CBCPD, COMP, ESR/CRP, Vit E, 24 hour urine copper, ceruloplasmin, ANA, ENA 11, DS-DNA, HIV,
paraneoplastic, FTA, lyme, thyroid antibodies, TSH/T4, GAD65, porphyria screen, urine heavy metal screen,
anti-gladin, NMDA, B12/MMA, Thiamine, UA/culture, urine GC mass spect, additional infectious labs if
immunosuppressed.
-LP (large volume, get opening pressure): Protein, glucose, cell count/diff, gram stain/culture, IGG index, Obands (not specific to MS), CRAG, ACE, cytology/flow, paraneoplastic, 14-3-3/tau (can be seen in CJD or
paraneoplastic), Whipple PCR, additional infectious labs if immunosuppressed.
-Studies: CT C/A/P, +/- whole body PET, MRI brain, LTM EEG, consider brain biopsy.
-Tx: Treat underlying etiology, if possible. If no diagnosis found, can trial IV solumedrol 1g x3-5 days and/or
IVIG in case it is autoimmune/paraneoplastic that is susceptible to immunosuppression. Establish DPOA, goals
of care, likely PT/OT/SLP consult (safety, and gauging level of impairment), social work support, ? G tube.