0:30

Hello and welcome back to the Neurotransmitters

0:32

, your source for everything related to clinical

0:34

neurology . Today we are

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continuing our internal medicine

0:39

board review neurology subtopic

0:42

review . So this is part five

0:44

, and today we are talking about cognitive

0:47

decline and dementia . So

0:49

, first of all , what is cognitive

0:51

impairment ? So this can be loosely

0:53

defined as a progressive loss

0:56

in cognitive function of at

0:58

least one major category , and

1:00

some of these major categories are things that we

1:02

might expect , things like memory , language

1:05

, executive function , that is , the ability

1:07

to complete complex tasks . Visual

1:09

, spatial function , such as the skills

1:11

you might need when you're navigating or driving

1:14

, and finally , behavior , our

1:16

social interactions . Now , when

1:18

the cognitive decline gets to the

1:20

point where it's involving more than one of these

1:22

areas , or is progressing to the

1:24

point where we are starting to have someone

1:26

lose their independent function

1:29

in these different arenas of life

1:31

, we would generally call this dementia

1:33

. So how do we approach these patients

1:35

? So , if the patient is coming to you

1:37

with concerns , or the family is coming to you with concerns

1:40

, or you , as the longstanding primary

1:42

care physician , have concerns

1:44

that the person you're seeing has cognitive

1:46

impairment , what are the things that we need

1:48

to do ? What are the clues that might

1:50

give us some inkling that there's something

1:52

going on . So , first of all , most

1:55

of the common dementias that we think about

1:57

are often a little bit more on the

2:00

longstanding , insidious

2:03

, chronic side of development . So often

2:05

over years , if we are

2:07

seeing a more of a subacute to acute process

2:09

, that has its own differential diagnosis and

2:12

we'll talk about some of those things later on . So

2:14

screening is not necessarily

2:16

recommended in all patients , but

2:19

over the age of 70 , it is a reasonable

2:21

thing to do some historical

2:23

facts that might prompt you to

2:25

do some screening . So if the family

2:27

is expressing concerns you

2:30

know someone's misspain bills or

2:32

they've been acting a little unusual compared to their

2:34

normal selves , right , if they're starting

2:36

to miss appointments , missing

2:38

their medications , taking too much of their medications

2:41

, if they've had an unexplained

2:43

change in weight usually weight loss

2:45

if they've become more withdrawn

2:47

, they're not engaging in their usual hobbies

2:49

or activities that they've been very routine

2:51

about being engaged in throughout their life

2:53

, that can sometimes be a little bit concerning

2:56

. And you do want to keep in mind that sometimes

2:58

the symptoms of depression in an elderly

3:00

person may be different than what we see

3:03

in someone who is younger . So you can

3:05

get a quote , unquote , pseudo dementia

3:07

from depression in some people , and

3:09

that is something to screen for also . So

3:11

we've talked about screening . What are some of our common

3:13

screening tools that we can use

3:16

? So I'll start with the shorter ones and we'll

3:18

kind of go into the longer ones . So the shorter

3:20

one is the mini cog , and this is essentially

3:22

a three word recall plus a clock

3:24

drawing test . I don't know how much longer

3:27

the clock drawing test will be useful , as we see

3:29

more and more people who aren't familiar with analog

3:31

clocks , but for now it is still

3:34

a useful test , and an abnormal screening

3:36

test can prompt us to look a little bit deeper as

3:38

well . Another screening test that is pretty common

3:40

is the mini mental status exam . This

3:43

one also is a little bit longer than

3:45

the mini cog but can still be done pretty

3:47

quickly 10 to 15 minutes by most people

3:49

. And lastly , we have the Montreal cognitive

3:52

assessment . It's a little bit harder

3:54

to do than the mini mental , but

3:56

it does have obviously a higher sensitivity

3:59

as far as that aspect of detecting

4:02

primarily Alzheimer's dementia

4:04

. So it is important to remember the limitations

4:07

of our tools , and so we'll talk about this as

4:09

we get to different types of dementia later on

4:11

. But there are some that may have more behavioral

4:14

or language predominant aspects , that

4:16

may not score as badly

4:18

as someone would say memory loss

4:20

in the setting of Alzheimer's dementia . So

4:23

let's say we've done our screening , we've found

4:25

some abnormalities suggestive of cognitive

4:27

impairment . Whether that is on our screening test or

4:30

by history , that prompts us to dig a little

4:32

bit deeper . So , as we mentioned earlier

4:34

, we want to look for reversible

4:36

versus irreversible or non reversible

4:38

causes . So we want to do some

4:40

screenings . We'll look for depression , which

4:43

can mimic dementia in some people . We

4:46

want to look for sleep disorders . If someone

4:48

has bad sleep that can sometimes manifest

4:50

as some cognitive impairment . Are

4:52

there new medications ? Are they

4:54

overusing alcohol , or is there

4:56

a family history of early onset or

4:59

a typical types of dementia ? Our next

5:01

step is doing a general neurologic examination

5:03

, including our cognitive screening , if

5:06

we haven't already done one , and generally

5:08

we're looking for other things that might

5:10

clue us into different types of dementia , looking

5:12

for signs of things like Parkinsonism , other

5:14

movement disorders , other physical

5:16

findings , muscle atrophy , weight loss

5:18

, etc . That might clue us into

5:21

a potential underlying cause or

5:23

even to a specific dementia

5:25

type syndrome . We also want to look

5:27

at medications . Are there medications on

5:29

board , especially recent ones , that

5:31

could cause a cognitive decline , especially

5:34

in someone who is a little bit older . So think

5:36

about polypharmacy , sedating

5:38

medications , anticholinergics , think about

5:40

your beer score criteria , all that kind of

5:42

stuff , and look for these kinds of medications

5:44

that may contribute to

5:46

some cognitive decline . As far as general

5:48

screening lab work that we want to get on pretty

5:50

much everybody we're usually talking about a complete

5:53

metabolic panel , a CMP , a

5:55

blood count , cbc , want to check vitamin

5:57

B12 , check a TSH , and

6:00

in those who are at risk you might consider

6:02

things like an RPR check for syphilis

6:04

or HIV . Everyone

6:06

is also going to be getting some sort of neuro

6:08

imaging , at least a CT head

6:11

, although an MRI brain would be preferable

6:13

just because it does show us a little bit

6:15

more detail in the brain perenchyma

6:17

. In those who have a little bit of an atypical

6:19

presentation but are otherwise fairly

6:22

typical , such as age of onset , being

6:24

over the age of 60 , and

6:26

more of a chronic insidious onset

6:29

, you might consider getting things

6:31

like an amyloid PET scan or even CSF

6:33

studies to look for amyloid

6:35

beta 42 or P-Tow

6:37

, total TOW levels and that can help clue

6:40

you into whether this is Alzheimer's , dementia or

6:42

some other process that bears further

6:44

investigation . I would very likely

6:46

consider these CSF studies or

6:48

amyloid PET scans , looking for

6:51

these abnormalities to support a diagnosis

6:53

of Alzheimer's in someone who presents with the

6:55

under the age of 55 to 60 , just to help

6:57

confirm that diagnosis and make sure there

6:59

isn't another diagnosis lurking in the background

7:02

that we missed In these younger patients . A sleep

7:04

study is also something reasonable to consider

7:06

, especially if you have a suspicion for undiagnosed

7:09

obstructive sleep apnea or other sleep

7:11

disorders , as impaired sleep

7:13

again can manifest with cognitive decline

7:15

in a fair number of people . Now

7:17

, if we have someone who has an atypical presentation

7:20

and we're usually talking more about this subacute

7:22

decline , we want to think about

7:24

our atypical ideologies

7:26

, so we are very often looking at these

7:29

more uncommon ideologies

7:31

. So we're wanting to check CSF studies

7:33

. We're looking for things like Kreuzfeld-Yakub

7:36

disease or CJD , checking 1433

7:39

protein , rt , quick checking

7:41

the amyloid and tile levels again just to

7:43

make sure this is not an atypical presentation

7:45

of Alzheimer's disease . Checking

7:47

perineoplastic syndromes , as a lot of these

7:49

can present with a subacute cognitive decline

7:52

. You have to think about different autoimmune ideologies

7:54

, various toxin exposures

7:56

again alcohol being the most common various

7:59

infections like HIV , lyme

8:01

disease , syphilis , and it's reasonable

8:03

to check an EEG for seizures also

8:06

, and an MRI of the brain is also essential

8:08

in these cases , as it can be very helpful

8:10

. You want to make sure there's no structural mass

8:13

lesions , in the frontal lobes in particular that could

8:15

be manifesting with a dementia-type

8:17

clinical picture . So let's talk about

8:19

our different classes of dementia that we're

8:21

considering amongst our more common causes

8:23

. So first of all , we have mild cognitive

8:26

impairment . So these are people who don't

8:28

necessarily meet the criteria for

8:30

dementia . They are relatively

8:32

able to continue doing their activities

8:34

of daily living . They're still able to maintain

8:37

a fair degree of independence . Essentially

8:39

, these declines have not

8:41

risen to the level where they

8:43

are having impairments in ADLs

8:45

. So mild cognitive impairment , or MCI

8:48

, can progress to dementia

8:50

. And it's estimated that 5% to 15%

8:52

annually of these patients will

8:55

progress from MCI to

8:57

dementia , most often Alzheimer dementia

8:59

. So let's talk about Alzheimer

9:01

disease . So it is the most

9:03

common form of neurodegenerative

9:05

dementia , representing about 60 to 80%

9:07

of cases , and the most common

9:10

form is a memory predominant form

9:12

or amnestic form of dementia

9:14

, although it can present in other ways as well

9:16

, and in these atypical cases is when you

9:18

might end up doing some of these more ancillary

9:20

testing to help confirm the diagnosis

9:22

. The greatest risk factor is

9:24

age , so the prevalence doubles

9:27

about every five years in the population

9:29

over the age of 65 . Some

9:31

other risk factors to be aware of . So

9:33

there are some genetic risk factors apolipoprotein

9:36

, e , epsilon 4 alleles

9:38

. So if someone has one or two copies

9:40

of this particular allele , it does

9:43

increase their lifetime risk for Alzheimer

9:45

disease . If there is a family

9:47

history of Alzheimer dementia , if

9:50

someone is female , if there is a

9:52

history of stroke , traumatic brain

9:54

injury , cardiovascular disease

9:56

or hearing loss , these are all

9:58

risk factors for developing dementia later

10:01

in life . Some factors that are thought to be

10:03

protective people who have higher

10:05

education levels , those who engage

10:07

in regular exercise , most often aerobic

10:09

, those who follow a heart-healthy

10:12

diet most of the evidence is for Mediterranean

10:14

diet and those who remain engaged

10:17

with cognitively stimulating activities

10:19

and maintain a good social network

10:21

, so avoiding things like depression

10:23

and social withdrawal . Those tend to

10:25

be protective for dementia as

10:27

we get older . The underlying pathophysiology

10:30

for Alzheimer's disease is thought to be related to

10:32

A beta plaques and neurofibrillary

10:34

tangles of tau . There are some anti-ameloid

10:37

medications that have been researched and

10:39

some of them are available to the public at

10:41

present . I'm not going to go too much into them now

10:43

because the guidelines with respect to

10:46

who are the best candidates and so forth

10:48

are still a little bit in flux at the time that we're recording

10:50

this . In terms of clinical presentation

10:52

, as we mentioned earlier , memory

10:55

issues are the most common presenting feature

10:57

. We can also see some language difficulties

11:00

. This may manifest as something very subtle

11:02

like some word finding , or it may be

11:04

something more flagrantly like a true aphasia

11:06

, although not usually quite

11:09

that severe , at least in the early stages

11:11

. There may also be some visual spatial

11:13

difficulties . People get lost while driving

11:15

. You may hear the story of a police officer

11:17

found someone sitting by the

11:19

side of the road in their car and they don't

11:21

know how they got there things of that nature . There

11:24

can often be poor insight

11:26

. Lack of insight is very common

11:28

as we get into the middle and

11:30

later stages of Alzheimer's disease

11:33

. Some of the other things

11:35

that we see later on in the progression

11:37

you'll see impaired executive dysfunction

11:39

, inability to do more complex tasks

11:41

. There can be mood and behavioral

11:44

changes . You might see sundowning

11:46

, agitation . Delusions can

11:48

also occur . Those who have

11:50

younger onset Alzheimer's disease may have

11:52

a little more non-memory predominant presentation

11:55

. So we may see more language or visual spatial

11:57

issues at the onset in these patients . In

12:00

terms of the testing for Alzheimer's disease , the

12:02

MRI of the brain may show decreased

12:05

hippocampal volume . That would be the classic finding

12:07

. At some centers you can get what

12:09

they call volume metric MRIs and

12:11

this will assess the relative size of the hippocampus

12:14

relative to the whole brain

12:16

volume . We can also see generalized

12:18

brain volume diminishment as well . Both

12:21

of those things can be seen with Alzheimer's , although

12:23

the MRI may not show anything definitively

12:25

, especially in the early stages . In addition

12:27

to the amyloid PET that we mentioned earlier

12:29

, you can also get an FDG PET and

12:32

this can be used to look for decreased activity

12:34

in the bilateral , parietal and or

12:36

temporal regions . Also

12:39

, as we mentioned earlier , csf testing can

12:41

be helpful if the diagnosis is uncertain

12:43

. We're looking at three specific protein numbers

12:46

here . We're looking at A beta 42

12:48

, which should be diminished in Alzheimer's , increased

12:51

tau and increased phosphorylated

12:54

tau . If these numbers line

12:56

up , this can be very specific when there

12:58

is some concern . Is this Alzheimer's dementia

13:00

or just an atypical presentation

13:02

versus another kind of dementia

13:04

process Related

13:06

to this ? A normal A beta 42

13:08

level has a high negative probability

13:11

for Alzheimer's disease . So if your

13:13

A beta 42 is normal on your

13:15

CSF testing , you should definitely be considering

13:18

alternative diagnoses besides

13:20

Alzheimer's disease . So what kind of

13:22

treatments can we offer people with Alzheimer's disease

13:24

. So there may be some limitations

13:26

, but we always want to check for any

13:28

possible contributing factors . So

13:30

making sure that the person is having good

13:32

sleep , make sure there's no other sleep disorders

13:35

obstructive sleep apnea can be a common

13:37

contributing factor in many of these patients make

13:40

sure that there isn't any untreated cardiovascular

13:42

disease , hypertension , diabetes

13:45

, et cetera all of these kind of cerebrovascular

13:48

cardiovascular risk factors , as there

13:50

is decent evidence that suggests that those

13:52

who , on autopsy , have Alzheimer's

13:54

disease very often will have some evidence

13:56

of vascular ischemic disease

13:58

to the brain as well . So making sure that we control

14:01

for those vascular risk factors can

14:03

theoretically be helpful . So what about

14:05

these other medications that are out there ? So

14:07

anyone who knows me knows I'm a little lukewarm

14:10

on them . But the different classes

14:12

that we talk about first of all we have acetylcholinesterase

14:15

inhibitors , and so first

14:17

we have the ones that are for mild to moderate dementia

14:19

in Alzheimer's disease , and these are things like denepousyl

14:22

, rivastigmine , galantamine , and

14:24

these have been shown to show modest improvement

14:26

in cognitive performance , but questionable

14:29

whether there's any clear improvement in ADLs

14:32

. They do have side effects . So you need to keep these

14:34

in mind , especially in patients who are already

14:36

dealing with other medical issues and might

14:38

be at risk for polypharmacy . So

14:40

our main side effects we have to watch out for

14:42

things like bradycardia , other cardiac

14:44

arrhythmias , especially if they have baseline

14:47

cardiac disease already . Gi side

14:49

effects like upset stomach , diarrhea

14:51

, dizziness , syncope , agitation

14:53

, vivid dreams can be reported in some

14:56

patients . So all of these things should be kept

14:58

in mind , especially if there's a temporal association

15:00

. And I am also a big advocate for

15:02

if you trial these medications and you

15:04

don't necessarily see a good improvement

15:07

clinically or by report from the

15:09

patient or their family , I tend to

15:11

be an advocate for again weaning

15:13

them off gradually . Another medication

15:16

we see used very often in these patients

15:18

is memantine . This is an NMDA

15:20

receptor antagonist and it's indicated for

15:22

moderate to severe dementia in Alzheimer's

15:24

again somewhat modest in response . And

15:27

, as mentioned earlier , there are some anti-amyloid

15:29

therapies out there , things like adjucanumab

15:31

, lecanumab , a lot of mabs

15:33

, if you will , and there are probably going to

15:35

be more in development as we go forward

15:37

in time . These have their own particular

15:39

complications , things like aria , which

15:42

is really beyond the scope of our conversation today

15:44

. So do check out some information about that if

15:46

you have patients asking you about it . Moving

15:48

on , let's talk about frontotemporal dementia

15:51

. So this comes in two main flavors

15:53

, if you will . So there's the behavioral

15:55

variant and then there is the aphasia

15:58

or primary progressive aphasia variant . So

16:00

with the behavioral variant , ftd

16:03

or frontotemporal dementia , we are primarily

16:05

seeing changes in personality and

16:07

behavior , usually much

16:10

earlier than we will other cognitive

16:12

changes , and the tricky thing with this

16:14

is that a lot of our screening tests

16:16

may not pick this up

16:18

. However , by history , their

16:20

functional impairment in their life

16:23

is often much worse than

16:25

you would think based off their performance on these

16:27

cognitive screens . So what kind of

16:29

behavioral changes are we really talking about

16:31

? So we see things like increased impulsivity

16:34

, apathy , impaired judgment

16:36

, obsessive , compulsive type tendencies

16:39

, and a lot of this will often lead to

16:41

a misdiagnosis with a psychiatric disorder

16:43

initially . We can also see things

16:45

like where people lose empathy , they

16:48

may become disinhibited , spending excessive

16:50

amounts of money . We may also

16:52

see a hyperorality , including

16:54

up to the point of eating non food items

16:57

, and a lot of these things , as you might

16:59

guess , can lead to legal issues as well

17:01

. There is also an association

17:03

with motor neuron disease , things like

17:05

ALS , with frontotemporal

17:07

dementia , so in particular

17:09

the C9-ORF72

17:12

mutation . So in patients who have

17:14

a diagnosis or suspected diagnosis

17:16

of FTD , you do want to check

17:18

out and see are they showing any signs of

17:20

ALS or other types of motor neuron

17:23

disorders that might be worrisome

17:25

things like weight loss , muscle atrophy , hyperreflexia

17:28

, etc . So there are some proposed

17:30

diagnostic criteria and

17:32

some of these include things like one , early

17:35

behavioral disinhibition . Two

17:37

, early apathy or inertia

17:39

. Three , early loss

17:41

of sympathy or empathy . Four

17:44

, perseverative or compulsive behaviors

17:46

. Five , hyperorality and dietary

17:49

changes . And six , neuropsychological

17:51

deficits in executive function with

17:53

relative sparing of memory and visual

17:56

spatial function . As far

17:58

as testing goes , neuropsychological

18:00

testing is indicated . Regular

18:02

screening is mostly intended for Alzheimer's

18:04

disease , as we mentioned earlier , and so we may

18:07

not catch these patients on our screening

18:09

tests . You do want to make sure these patients

18:11

get some sort of neuroimaging . Mri brain again

18:13

is ideal to make sure that there are no frontal

18:16

lobe lesions like a history of traumatic brain injury

18:18

or a mass , and CSF

18:20

testing can be helpful to make sure it's not an atypical

18:23

presentation of something like Alzheimer's

18:25

disease . So making sure those A-beta-42

18:27

levels are normal . Treatment for these patients

18:29

is mostly symptomatic and working in

18:32

tandem with a psychiatrist or , even better

18:34

, a geriatric psychiatrist , can

18:36

be very helpful for managing a lot of the

18:38

comorbidities with this particular dementia

18:40

. Now , that was behavioral variant

18:42

FTD . The other one is

18:44

primary progressive aphasia and

18:47

, as the name would suggest , this is a progressive

18:49

worsening in language as the primary

18:52

presenting symptom and this also

18:54

tends to come in a couple different variants

18:56

. So we have non-fluent or

18:58

agrammatic and this is trouble with language

19:00

production primarily , and then

19:02

we have fluent or semantic and

19:04

this is usually more trouble with comprehension

19:07

. You may see some more behavioral

19:09

issues with this particular type In

19:11

terms of evaluation on neuropsychological

19:13

testing . They have difficulty with word

19:15

repetition , language repetition , timed

19:17

word production tasks like how many

19:19

words can you produce in one minute that

19:22

begin with the letter F , and object naming

19:24

. These tend to be the things that they struggle with the most

19:26

. Sometimes the MRI of the brain

19:28

will show atrophy of the frontal

19:30

or temporal regions . You know frontal temporal

19:32

dementia right . This can sometimes be called knife

19:35

edge atrophy and will be very

19:37

prominent in particular along the anterior

19:39

portion of the temporal lobe . If the MRI

19:41

of the brain is normal , you can also get functional

19:44

imaging with things like an FDG , pet

19:46

or even a SPECT and

19:48

that can be helpful to show if there is involvement

19:50

of the dominant temporal lobe . Treatment

19:52

is again often supportive and it does involve

19:54

the use of speech therapists and or

19:56

assistive language devices , as appropriate

19:59

, next up two entities that

20:01

are rather closely related to one another

20:03

Dementia with Lewy bodies and

20:05

Parkinson's disease related dementia

20:07

. So if motor symptoms tend

20:09

to develop before the cognitive symptoms

20:11

, this usually leads towards a diagnosis of

20:13

Parkinson's disease . If we have

20:15

, however , cognitive changes one to two

20:18

years before motor changes , this

20:20

is classically thought to be dementia with

20:22

Lewy body disease or DLB . So

20:24

DLB is the second most

20:27

common types of neurodegenerative dementia

20:29

after Alzheimer's disease , and both

20:31

Parkinson's and Lewy body

20:33

is thought to be related to alpha-synuclein

20:37

protein abnormalities . The

20:39

main features that we see with Lewy body dementia

20:41

are obviously dementia . There are

20:43

often Parkinsonian features , things like

20:45

bradykinesia , slowed movements , gait

20:48

difficulties . We can also see orthostatic

20:50

hypotension or other autonomic dysfunctions

20:53

. The unique thing about Lewy

20:55

body dementia is that you tend to get earlier

20:57

onset visual hallucinations . You

21:00

also have these very severe at

21:02

times fluctuations in attention . Rem

21:05

sleep behavior disorder can proceed

21:07

both Lewy body and Parkinson's

21:09

disease by , sometimes years . A

21:12

unique and kind of idiosyncratic reaction

21:14

that we can sometimes see with dementia with Lewy bodies

21:16

is severe neuroleptic

21:19

drug sensitivity . So you really

21:21

want to avoid antipsychotic medications

21:24

in this population as it may lead to

21:26

neuroleptic malignant syndrome In real

21:28

life . There are always exceptions , but these need

21:30

to be treated as unique cases . Every time

21:32

On the test you will avoid

21:34

the antipsychotics . What kind of treatments

21:36

can we offer patients with DLB ? So

21:39

acetylcholonesterase inhibitors may

21:41

be effective for some patients . Other

21:43

mood related medications such as antidepressants

21:45

and other interventions may be needed , depending

21:48

on the individual person . Next

21:50

up we have vascular dementia or vascular

21:53

cognitive impairment . This is a

21:55

very common cause and is , as

21:57

I mentioned earlier , often seen in

21:59

autopsy pathology with Alzheimer's

22:02

disease . So the risk does increase

22:04

with age . Very often there may

22:06

be a clinical history of stroke or

22:08

they may have had quote unquote silent strokes

22:11

that you only note on imaging . Very

22:13

often they will have poorly controlled cardiovascular

22:16

cerebral vascular risk factors as well

22:18

, signs that may help you differentiate

22:20

Alzheimer's disease from vascular dementia

22:22

. If they obviously have focal neurologic

22:25

deficits , that suggests maybe a stroke as

22:27

an underlying cause . If they

22:29

have earlier gait impairment or

22:31

if they have earlier onset of pseudo-bulbar

22:33

affect , this emotional incontinence

22:35

, laughing or crying inappropriately

22:38

, or laughing or crying with absence

22:40

of emotional content . They don't

22:42

feel happy or sad as they are laughing

22:45

or crying respectively , and so

22:47

that can sometimes be a clue

22:49

that maybe they've had a stroke in different areas of the brain

22:51

. The MRI of the brain is very important

22:53

in making this diagnosis , as we are

22:55

looking for evidence of white matter disease

22:58

, micro hemorrhages , other

23:00

evidence of lacuna or cortical based

23:02

infarcts , things that show that this

23:04

person has suffered different vascular

23:06

insults to the brain . Treatment

23:09

wise , again , we want to control

23:11

those vascular risk factors to the best

23:13

extent we can . Other medications you

23:15

can try acetylcholinesterase inhibitors . They may

23:17

have some modest efficacy . Amantine

23:20

also could be something reasonable to try in appropriate

23:22

adaptations . Next up we

23:24

have normal pressure hydrocephalus or

23:26

NPH , and this consists

23:28

of the triad of gait changes

23:31

, often wide based , urinary

23:33

incontinence and cognitive impairment

23:35

, usually some slowing and some executive

23:37

impairment . This is often remembered with the three

23:40

W's wet , wacky and wobbly . It is important

23:43

to remember that you may see some Parkinsonism

23:45

on exam in these patients as well . So

23:47

bradykinesia or rigidity may also

23:49

be seen . And diagnosis

23:52

wise we want to start with brain imaging

23:54

, so a CT or brain MRI

23:57

, and what we're really looking for is ventricular

23:59

enlargement and there are other features

24:01

that can be looked at kind of beyond the scope of our

24:03

talk today . Testing

24:06

wise the main test that we are doing

24:08

after imaging is a high volume lumbar puncture and what

24:10

we're looking for is we want

24:12

a timed gait assessment

24:14

pre and post lumbar puncture

24:17

to see

24:19

is there clear , definite

24:21

improvement in their ambulation ? And people for whom there is a high suspicion

24:25

for NPH . But the LP results are somewhat

24:27

equivocal . A lumbar drain trial can also be done . Treatment

24:32

wise , if they have a clear response

24:34

to CSF diversion , a VP shunt of ventricular

24:36

peritoneal shunt

24:38

is recommended and this tends to improve

24:40

gait , more so than the other two symptoms the urinary incontinence

24:43

and the cognitive decline . The longer the cognitive decline

24:45

has been present , the less it tends to

24:47

improve with shunt placement

24:50

. Another entity it's important to know

24:52

about is chronic

24:55

traumatic encephalopathy , or CTE , in the

24:57

old days called dementia apugia . So

25:00

historically it's been associated with folks who get

25:02

hit in the head a lot , so boxers , american

25:05

football players , people who have a history

25:07

of repeat concussions or even subconcussive head

25:10

injuries , and this tends

25:12

to affect the frontal and temporal lobes the most Often these

25:16

people will present , with behavioral changes , things like

25:18

apathy , irritability , impulse

25:20

control issues , emotional dysregulation

25:23

or outbursts , depression . You can also see some associated

25:26

Parkinsonism , such as bradykinesia

25:28

or gait changes . Treatment is often symptomatic antidepressants

25:32

. If they have signs of Parkinsonism you might try some Parkinson's

25:35

meds , although you

25:37

do have to watch out for that worsening impulsivity with some

25:39

of these dopamine based therapies

25:41

. You have to monitor for suicide

25:43

risk . You can also try different acetylcholinesterase inhibitors

25:47

as well . One thing you've likely noticed

25:49

about most of these different dementia syndromes

25:51

is that neurobehavioral symptoms can be

25:53

very disabling and very often these

25:55

can lead to placement in a nursing facility as opposed

25:58

to being able to stay at home with family or

26:00

with a loved one . So very often

26:02

we need to treat these in some fashion . So

26:04

antidepressant agents are often used

26:06

. Acetylcholinesterase inhibitors can also

26:08

be tried . You generally want to

26:10

avoid benzodiazepines , as this can

26:13

lead to sedation and increased fall risk

26:15

. You also generally want

26:17

to avoid antipsychotics . They do have

26:19

a black box warning for increased mortality

26:21

in older people . If you are

26:23

going to use them , if they are appropriate someone's having

26:25

hallucinations , delusions , things like that then

26:28

you want to start with low doses and

26:30

you generally want to lean towards the newer

26:32

generation agents . It is also

26:35

recommended to get an EKG prior

26:37

to initiation to make sure that you do not have any

26:39

QTC interval prolongation

26:41

. Let's shift gears just a little bit . So

26:43

far we've been talking primarily about kind of these more

26:45

slower onset types of dementia

26:48

. But what about rapidly progressive

26:50

dementia . The differential diagnosis

26:52

is a little bit different . So , as we

26:54

mentioned briefly earlier , things

26:56

like Kreuzfeld-Yakov disease , perineoplastic

26:58

syndromes , different autoimmune syndromes

27:01

, whether those are systemic or central

27:03

nervous system only , things such as

27:05

chogrens , sarcoidosis , butchette

27:07

, cns vasculitis , multiple

27:09

sclerosis , adem , acute

27:11

dissemination , cephalomyelitis , other types of CNS

27:14

demyelinating disorders and other

27:16

types of infectious things that can affect the brain

27:18

. A special word about Kreuzfeld-Yakov

27:21

disease or CJD . It is a

27:23

prion disorder . It is potentially transmissible

27:25

. The time from the onset of symptoms

27:28

to death is often around 12

27:30

months . In about four out of five patients

27:32

there are some associated clinical

27:34

findings , such as myoclonus , often

27:36

startle myoclonus , gait

27:38

issues and a disordered sleep

27:41

wake cycle . The MRI of the

27:43

brain can be very helpful as in some

27:45

patients it will show restricted diffusion

27:48

, often in the cortex or the basal

27:50

ganglia . Eeg can

27:52

also be helpful in some patients as it may

27:54

show generalized periodic sharp waves

27:56

or generalized periodic discharges

27:58

. Csf testing also very

28:01

helpful . You're looking for two specific

28:03

abnormalities 1433

28:05

, which is an abnormal protein , or RT

28:08

, quick , and this is looking for prion

28:11

disease specifically . Lastly , I

28:13

want to mention delirium , not a

28:15

typical dementia or cognitive impairment

28:17

disorder , but it is a risk

28:19

factor for dementia and it does present

28:22

with cognitive impairment . So

28:24

we tend to define it as a waxing and waning

28:26

of someone's normal mental status

28:28

. So we can see alterations in sleep

28:30

, attention arousal . It

28:33

can include things such as disorganized thoughts

28:35

, delusions , hallucinations , impaired

28:38

attention , sleep dysregulation . You

28:40

can see myoclonus or asterixis or

28:42

both , and sometimes a restlessness

28:45

. There are different tools to assess

28:47

for delirium . One of the better ones is the

28:49

confusion assessment method , the CAM

28:52

or CAM . Delirium can be tricky

28:54

as it can be related to nearly any

28:56

medical condition . Some common things

28:58

that we want to look for is the person on

29:00

sedating medications or polypharmacy

29:02

, in particular psychotropics

29:04

, pain medications , different anti seizure

29:06

medications , right Things that work on the CNS , different

29:09

antibiotics ? Are they in

29:11

alcohol withdrawal ? Do they have

29:13

baseline CNS disease , such

29:15

as a history of seizures , stroke , intracranial

29:18

hemorrhages or traumatic brain injury ? Do

29:20

they have other metabolic disorders , whether

29:22

chronically or acutely ? Hyper

29:24

or hypoglycemia , hypoxemia

29:27

, hypercarbia , other types of organ

29:29

failure , whether chronically or acutely , such

29:31

as liver or kidney issues ? Are

29:33

they B12 or B1 deficient

29:35

? Is their blood pressure incredibly elevated

29:37

? Is this a hypertensive emergency ? Are

29:39

there concerns for underlying infections , whether

29:42

that's someone who maybe has a baseline dementia with

29:44

a UTI ? Do they have respiratory

29:46

infections , meningitis or encephalitis

29:49

? Is there concern for sepsis ? Did they

29:51

recently undergo trauma or have surgery

29:53

? Are they in an ICU setting some

29:55

place ? That's going to contribute more to

29:57

sleep wake dysregulation that's going to predispose

30:00

them towards delirium . Do they have uncontrolled

30:02

pain , blood loss , etc . Again

30:05

, generally you want to avoid the use of benzodiazepines

30:07

unless you're treating alcohol withdrawal

30:10

and you do generally want to avoid the

30:12

use of antipsychotics . You should always

30:14

be looking for the underlying cause of

30:16

delirium . This may require neuroimaging

30:19

to assess for other causes such as stroke

30:21

or CNS infections , and EEG may also

30:23

be reasonable if there is a clinical concern

30:25

for seizures . Although very often in the ICU

30:28

setting , nonconvulsive seizures can be common

30:30

. For those who are interested in learning more about delirium

30:32

, I strongly recommend checking out the Psychiatry

30:35

Boot Camp podcast about

30:37

delirium with Dr Mark Oldham . It

30:39

was a great interview , very entertaining , strongly

30:42

recommended . As always , this was not intended

30:44

to be a comprehensive review but a

30:46

quick overview intended for those who are reviewing

30:49

for their internal medicine boards , so do

30:51

forgive me if I left out particular

30:53

points . This is not intended to be a deep

30:55

dive on each one of these , as that could fill hours

30:57

on each one of these particular subjects , but

31:00

if you did enjoy this podcast , I would appreciate

31:02

getting a five-star review from you on Apple

31:04

, itunes , spotify . Wherever you are getting

31:06

your podcasts , leave us a comment , send

31:08

us an email . You can find us online at

31:11

theneurotransmitterscom . You

31:13

can also find me on X at

31:15

Dr Kentris D-R-K-E-N-T-R-I-S

31:17

, or our main account at

31:19

Neuro Underscore Podcast . Thank

31:21

you again for listening this far . I really appreciate

31:24

you taking the time to listen to all this stuff

31:26

about dementia , and I'm sure your patients will appreciate

31:28

it too . So , as always , thank you and

31:30

we'll see you next time .