Dementias

Question 1

AD Genetics What is LOAD

What % is late onset?
What % are APOE4?

-

Answer 1

LOAD (Late Onset AD), by contrast, is associated with the APOE gene.

• 95% of AD is sporadic or late onset AD
• Although over 60% of AD patients are APOE4 positive, many patients do not carry this gene and it is clearly not deterministic. Recent large-scale and well-powered genomewide association studies (Hollingworth et al., 2011; Naj et al., 2011) have identified additional genes associated with LOAD, but to date all have small odds ratios and are not useful in predicting who will develop AD or at what age.

Question 2

MCI AD Presentation

Answer 2

• prominent impairment in episodic memory (i.e., amnestic-MCI), but other patterns of cognitive impairment can also progress to AD dementia over time (e.g., executive dysfunction/ nonamnestic MCI or multidomain MCI).
• positive biomarker for the molecular neuropathology of AD (e.g., lower CSF Aß-42 and raised CSF tau measures), this provides the highest level of certainly that over time the individual will progress to AD dementia.

This level of certainty would be increased even further if the individual has positive topographic biomarker evidence of AD.

However, the absence of such topographic biomarker evidence (or equivocal or normal findings) is still consistent with the highest level of certainty that the individual will progress to AD dementia over time.

Question 3

Dementia Prevalance

Answer 3

• 60 and above found a rate of 1.5% for most regions

- Double every 4 years

Question 4

DLB Attention Fluctuation

Answer 4

• typically delirium-like,
• occurring as spontaneous alterations in cognition, attention, and arousal. They include waxing and waning episodes of behavioral inconsistency, incoherent speech, variable attention, or altered consciousness that involves staring or zoning out.

Question 5

DLB biomarkers

Answer 5

• Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET. Abnormal (low uptake) 123iodine-MIBG myocardial scintigraphy.
• Polysomnographic confirmation of REM sleep without atonia.
• Relative preservation of medial temporal lobe structures on CT/MRI scan.
• Generalized low uptake on SPECT/PET perfusion/metabolism scan with reduced occipital activity 6 the cingulate island sign on FDG-PET imaging.
• Prominent posterior slow-wave activity on EEG with periodic fluctuations in the pre-alpha/ theta range.

Question 6

DLB REM Sleep Behaviour Disorder

Answer 6

RBD is a parasomnia man- ifested by recurrent dream enactment behavior that includes movements mimicking dream content and associated with an absence of normal REM sleep ato- nia.

It is particularly likely if dreams involve a chasing or attacking theme, and if the patient or bed partner has sustained injuries from limb movements.

Question 7

DLB Visual Hallucinations

Answer 7

Recurrent, complex visual hallucinations occur in up to 80% of patients with DLB and are a
frequent clinical signpost to diagnosis.
They are typically well-formed, featuring people, children, or animals, sometimes accompanied by related phenomena including passage hallucinations, sense of presence, and visual illusions.

Question 8

DLB Vs AD

Answer 8

Visual hallucinations and agnosia early in the course of a dementing illness can help distinguish DLB from AD.

DLB: prominent attention, executive, and visuospatial impairment rather than memory deficits early in its course.

Visual hallucinations and agnosia early in the course of a dementing illness can help distinguish DLB from AD.

DLB: prominent attention, executive, and visuospatial impairment rather than memory deficits early in its course.

The dementia syndrome of DLB is similar to AD, and pathological studies have revealed the presence of Lewy bodies in as many as 20% of AD cases at autopsy.

Question 9

MCI AD Conversion

Answer 9

• The past decade of research has indicated that individuals meeting criteria for late MCI in a clinical setting convert to AD at a rate of about 12% to 15% per year. Carriers of the epsilon 4 allele of the APOE gene are at particularly enhanced risk for progression.

Question 10

Parkinsonism

Answer 10

tremor,
bradykinesia,
rigidity,
postural instability.

Question 11

VCI (Vascular Cognitive Impairment)

Answer 11

• NCD as a continuum of cerebrovascular disease (CVD) due to small and large vessel involvement,
• fluctuating or stepwise course as well as more focal or patchy neurological and neuropsychological deficits is much more likely to reflect VCI due to CVD than AD or other neurodegenerative dementias.
• Early treatment of hypertension, hyperlipidemia, and other features of CVD can help prevent further progression (although Ricker questioned this).
• However, the relationship between AD and VCI is complex, in part because AD and CVD are both common and coexist frequently and because evidence suggests that small strokes or risk factors for vascular disease may lead to increased clinical expression of AD

Question 12

VCI DSM Criteria

Answer 12

• NCD with clinical features consistent with vascular etiology (onset of the cognitive deficits is temporally related to vascular events;
• decline is prominent in complex attention, including processing speed, and frontal-executive function;
• evidence of CVD from history, physical examination and/or neuroimaging). In addition, the NCD is not better explained by another brain disease or systemic disorder.

Question 13

VCI MRI Findings

Answer 13

Enhanced MRI techniques reveal cerebral microbleeds, which are found in up to a quarter of older adults and a third of patients with AD

Question 14

DLB Core Features

Answer 14

ESSENTIAL: dementia, defined as a progressive cognitive decline of
sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention, executive function, and visuoperceptual ability may be especially prominent and occur early-

• Fluctuating cognition with pronounced variations in attention and alertness. -
• Recurrent visual hallucinations that are typically well formed and detailed.
• REM sleep behavior disorder, which may precede cognitive decline.

One or more spontaneous cardinal features of parkinsonism

Question 15

DLB Supportive features

Answer 15

Severe sensitivity to antipsychotic agents; -

postural instability; repeated falls; syncope or other transient episodes of unresponsiveness;

• severe autonomic dysfunction, e.g., constipation, orthostatic hypotension, urinary incontinence; hypersomnia; hyposmia; hallucinations in other
  modalities; systematized delusions; apathy, anxiety, and depression

Question 16

DLB Biomarkers

Answer 16

Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET.

Abnormal (low uptake) 123iodine-MIBG myocardial scintigraphy.

Polysomnographic confirmation of REM sleep without atonia.

Question 17

DLB vs. Parkinson disease

Answer 17

DLB should be diagnosed when dementia occurs before or concurrently with parkinsonism.

The term Parkinson disease dementia (PDD) should be used to describe dementia that occurs in the context of well-established Parkinson disease.

Question 18

Mild Neurocognitive Disorder

Answer 18

Evidence of minor cognitive decline from a previous level of performance in one or more of the domains outlined above based on:

reports by the patient or a knowledgeable informant, or observation by the clinician, of minor levels of decline in specific abilities as outlined for specific domains described in Item 1 in the Major Neurocognitive Disorder list;

AND
mild deficits on objective cognitive assessment, typically 1.0 to 2.0 standard deviations below the mean (or in the 2.5th to 16th percentile) of an appropriate reference population (i.e., age, gender, education, premorbid intellect, and culturally adjusted). When serial measurements are available, a significant (e.g., 0.5 SD) decline from the patient’s own baseline would serve as more definitive evidence of decline. The cognitive deficits are not sufficient to interfere with independence (instrumental ADLs are preserved), but greater effort and compensatory strategies may be required to maintain independence.

The cognitive deficits do not occur exclusively in the context of a delirium.

The cognitive deficits are not wholly or primarily attributable to another Axis I disorder (e.g., major depressive disorder, schizophrenia).

Question 19

Major Neurocognitive Disorder

Answer 19

Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (enumerated as complex attention, executive ability, learning and memory, language, visual constructional-perceptual ability, and social cognition) based on: reports by the patient or a knowledgeable informant, or observation by the clinician, of clear decline in specific cognitive abilities;

AND clear deficits in objective assessment of the relevant domain, which is typically > 2.0 standard deviations below the mean (or below the 2.5th percentile) of an appropriate reference population (i.e., age, gender, education, premorbid intellect, and culturally adjusted).

The cognitive deficits are sufficient to interfere with independence; at a minimum requiring assistance with instrumental activities of daily living (ADLs; and i.e., more complex tasks such as finances or managing medications).

The cognitive deficits do not occur exclusively in the context of a delirium. The cognitive deficits are not wholly or primarily attributable to another Axis I disorder (e.g., major depressive disorder, schizophrenia).

Question 20

DLB Neuropsych

Answer 20

Pure DLB involves more

• prominent attention,
• executive,
• visuospatial - impairment rather than memory deficits early in its course.

Question 21

FTD presentation

Onset
Early Sx.
Neuro Sx.

Answer 21

• Onset of frontal dementias is typically much earlier than sporadic AD (often ages 50–60),60), but FTD can occur among younger or older individuals.
• Characterized in their early stages by changes in personality, executive dysfunction, deterioration of social skills, emotional blunting, behavioral disinhibition, and language abnormalities.
• difficulties with memory, apraxia, and additional behavioral disturbances (i.e., apathy or extreme agitation) appear later in the disease course.

Question 22

FTD neuroanatomy

Answer 22

Prominent frontal or temporal atrophy or both,

diagnosis is confirmed by an autopsy finding of Pick inclusion bodies.

FTD tauopathies (e.g., Pick’s disease, corticobasal degeneration, progressive supranuclear palsy),

OR

nontauopathies (lacking distinctive histology), and FTD with ubiquitin–immunoreactive inclusions (+/− motor neuron disease).

Question 23

MCD due to AD

Answer 23

Insidious onset, in that symptoms have a gradual onset over months to years, and the onset was not sudden over hours or days; and, clear-cut history of worsening cognition by report or observation; and cognitive deficits are evident on history and examination in one of the two categories, including the following: Amnestic presentation. The most common syndromic presentation of AD dementia.

The deficits should include impairment in learning and recall of recently learned information. There should also be evidence of cognitive dysfunction in other cognitive domains.

Nonamnestic presentation:
Language presentation: The most prominent deficits are in word-finding, but dysfunction in other cognitive domains should be present.
Visual presentation: The most prominent deficits are in spatial cognition, including object agnosia, impaired face recognition, simultanagnosia and alexia. Deficits in other cognitive domains should be present. Executive presentation: The most prominent deficits are in impaired reasoning, judgment and problem solving. Deficits in other cognitive domains should be present.

Question 24

Probable AD Dementia

Answer 24

clinical and cognitive criteria for AD dementia AND without evidence of any alternative diagnoses, in particular, no significant cerebrovascular disease.

Documented decline: Has evidence of progressive cognitive decline on subsequent evaluations based on information from informants and cognitive testing in the context of either brief mental status examinations or formal neuropsychological evaluation;

OR Biomarker positive: Has one or more of the following supporting biomarkers. Low CSF Aβ42, elevated CSF tau or phospho tau Positive amyloid PET imaging Decreased FDG uptake on PET in temporoparietal cortex Disproportionate atrophy on structural MRI in medial temporal lobe (especially hippocampus), basal and lateral temporal lobe, and medial parietal isocortex; OR Mutation carrier: Meets clinical and cognitive criteria for AD dementia and has a proven AD autosomal dominant genetic mutation (PSEN1, PSEN2, APP).

Question 25

Possible AD Dementia

Answer 25

Atypical Course: Evidence for progressive decline is lacking or uncertain but meets other clinical and cognitive criteria for AD dementia; OR Biomarkers Obtained and Negative: Meets clinical and cognitive criteria for AD dementia but biomarkers (CSF, or structural or functional brain imaging) do not support the diagnosis;

OR Mixed Presentation: Meets clinical and cognitive criteria for AD dementia but there is evidence of concomitant cerebrovascular disease; this would mean that there is more than one lacunar infarct; or a single large infarct; or extensive and severe white matter hyperintensity changes; or evidence for some features of dementia with Lewy bodies (DLB) that do not achieve a level of a diagnosis of probable DLB.

Question 26

A Note on Biomarkers

Answer 26

biomarkers, like those that associate with amyloid levels, are specific to etiology but do not associate well with disease burden (Knopman et al., 2013). Others, like levels of tau in CSF, are not etiologically specific but do associate with degree of brain involvement and therefore with cognitive, behavioral, and functional changes. Current etiological and disease burden biomarkers are listed in Table 30.2. Although used primarily to define syndrome phases, cognition itself can be thought of as a disease burden biomarker as neuropsychological measures meet the definition of a biomarker

Question 27

Earliest neuropsych changes in AD and differential from lewy and from FTD

Answer 27

The pattern of performance on measures of episodic and semantic memory, visuospatial skills, and specific aspects of attention, working memory, and executive function, is important in the differential diagnosis of AD compared to other, predominantly subcortical, dementias. The general profile of impairment in the cortical dementia of typical AD is characterized by prominent deficits in new learning and delayed recall with additional challenges to language and semantic memory, abstract reasoning, executive functions, with possible later involvement of attention, constructional and visuospatial abilities

Episodic memory changes have long been documented to appear in AD prior to the diagnosis of either dementia or MCI

On average, individuals with preclinical AD show a significant decline in the retention aspects of episodic memory about four to five years prior to diagnosis

AD patients exhibit a more pronounced impairment on category fluency than letter fluency, suggesting a breakdown in semantic knowledge access in AD (Henry, Crawford, & Phillips, 2004). AD patients also tend to make semantically based errors on confrontation naming (Salmon & Filoteo, 2007) though naming impairments are not consistently present in AD

Early executive function impairments in AD occur in cognitive processes involved in divided attention, working memory, concept formation, and problem solving

Deficits in visuospatial skills and constructional praxis, though commonly observed in AD, tend to emerge later in the course of the disease (e.g., Mielke et al., 2007) except in the visual variant of AD, also known as posterior cortical atrophy.

Behavioral symptoms can contribute to differential diagnosis of dementia type, and it is often the absence or late onset of these symptoms that characterizes AD (McKeith et al., 2005). For example, disinhibition is often an early symptom of behavioral variant fronto-temporal dementia but a late symptom in AD. Moreover, late onset hallucinations is one feature distinguishing AD from Lewy body disease, in which hallucinations are an early phenomena

Question 28

Va MCI

Answer 28

diagnosis of VaMCI may be further described as single domain amnestic, amnestic plus other domains, nonamnestic single domain, and nonamnestic multiple domains based on the cognitive domain( s) impaired by vasculopathy. These criteria require assessment of the same four domains listed earlier (executive/ attention, memory, language, and visuospatial functions). Instrumental ADLs could be normal or mildly impaired, independent of the presence of motor/ sensory symptoms.

Question 29

Probable VaMCI

Answer 29

There is cognitive impairment and imaging evidence of cerebrovascular disease, and There is a clear temporal relationship between a vascular event (e.g., clinical stroke) and onset of cognitive deficits; or, There is a clear relationship in the severity and pattern of cognitive impairment and the presence of diffuse, subcortical cerebrovascular disease pathology (e.g., as in CADASIL). There is no history of gradually progressive cognitive deficits before or after the stroke that suggests the presence of a nonvascular neurodegenerative disorder.

Question 30

Possible VaMCI

Answer 30

There is cognitive impairment and imaging evidence of cerebrovascular disease, but, There is no clear relationship (temporal, severity, or cognitive pattern) between the vascular disease (e.g., silent infarcts, subcortical small-vessel disease) and onset of cognitive deficits.

There is insufficient information for the diagnosis of VaMCI (e.g., clinical symptoms suggest the presence of vascular disease, but no CT/ MRI studies are available). Severity of aphasia precludes proper cognitive assessment. However, patients with documented evidence of normal cognitive function (e.g., annual cognitive evaluations) before the clinical event that caused aphasia could be classified as having probable VaMCI.

There is evidence of other neurodegenerative diseases or conditions in addition to cerebrovascular disease that may affect cognition, such as A history of other neurodegenerative disorders (e.g., Parkinson disease, progressive supranuclear palsy, dementia with Lewy bodies); The presence of AD pathology is confirmed by biomarkers (e.g., PET, CSF, amyloid ligands) or genetic studies (e.g., PS1 mutation); or, A history of active cancer or psychiatric or metabolic disorders that may affect cognitive function.

Question 31

Probable VaD

Answer 31

Cognitive impairment and imaging evidence of cerebrovascular disease.

There is a clear temporal relationship between a vascular event (e.g., clinical stroke) and onset of cognitive deficits, or there is a clear relationship in the severity and pattern of cognitive impairment and the presence of diffuse, subcortical cerebrovascular disease pathology (e.g., as in CADASIL).

There is no history of gradually progressive cognitive deficits before or after the stroke that suggests the presence of a nonvascular neurodegenerative

Relates to course of onset!

Question 32

Possible VaD

Answer 32

There is cognitive impairment and imaging evidence of cerebrovascular disease, but:

There is no clear relationship (temporal, severity, or cognitive pattern) between the vascular disease (e.g., silent infarcts, subcortical small-vessel disease) and the cognitive impairment.

There is insufficient information for the diagnosis of VaD (e.g., clinical symptoms suggest the presence of vascular disease, but no CT/ MRI studies are available).

**Severity of aphasia precludes proper cognitive assessment.

However, patients with documented evidence of normal cognitive function (e.g., annual cognitive evaluations) before the clinical event that caused aphasia could be classified as having probable VaD.

There is evidence of other neurodegenerative diseases or conditions in addition to cerebrovascular disease that may affect cognition, such as the following. A history of other neurodegenerative disorders (e.g., Parkinson disease, progressive supranuclear palsy, dementia with Lewy bodies);

The presence of AD biology is confirmed by bio-markers (e.g., PET, CSF, amyloid ligands) or genetic studies (e.g., PS1 mutation); or A history of active cancer or psychiatric or metabolic disorders that may affect cognitive function.

Question 33

On pure AD/VD

Answer 33

Some investigators express doubt that cognitive profiles are useful in separating AD from VaD , not only because cerebrovascular disease contributes to some of the same domains of cognitive impairment as in AD (e.g., executive function), but also because of the common occurrence of mixed pathologic processes.

Some authors suggest that many cases of dementia meeting the original criteria for the clinical diagnosis of probable AD have been shown to arise from mixed pathologies (Schneider, Arvanitakis, Leurgans, & Bennett, 2009; Sonnen et al., Some investigators express doubt that cognitive profiles are useful in separating AD from VaD , not only because cerebrovascular disease contributes to some of the same domains of cognitive impairment as in AD (e.g., executive function), but also because of the common occurrence of mixed pathologic processes.

Question 34

Neuropsychology of Vascular Dementia/Differential Dx. of AD vs. VD.

Answer 34

Cortical versus subcortical neuropsychological patterns are helpful in considering diagnoses of “pure” AD versus VCI versus “mixed” pathologies if there is sensitivity to the notion that cognitive domains may have subcomponents that are differentially impaired with the cortical/ subcortical heuristic.

• VaD are generally more impaired than those with AD on tests of executive functions, whereas patients with AD are more impaired than those with sub-cortical VaD on tests of episodic memory
• executive dysfunction is the most conspicuous deficit associated with subcortical VaD, perhaps because the subcortical pathology frequently interrupts fronto-subcortical circuits that mediate this aspect of cognition.

VaD patients with significant white matter abnormalities on imaging demonstrate a profile of greater executive dysfunction and visuoconstructive impairments than impairment of memory and language abilities.

VaD patients tend to demonstrate better episodic memory performance relative to patients with AD

AD worse memory earlier; VD worse memory later.

Opposite for exec.

• Patients with cerebral small vessel disease perform worse on processing speed measures (e.g., Digit Symbol) than patients with prodromal AD
• cerebral small vessel disease also perform less accurately on tests designed to measure the capacity to establish and maintain a mental set through a series of tasks and on measures of mental manipulation and temporal reordering

AD variant patients (i.e., not PCA) perform better than VaD patients on the Rey-Osterrieth Complex Figure Test (ROCF) copy portion, such that VaD patient drawings tend to be more fragmented and contain numerous perseverations and omissions. VaD patients also make more clock drawing errors than AD patients

Question 35

Lewy Body Disease less likely if…

Answer 35

A diagnosis of DLB is less likely in the following circumstances: In the presence of cerebrovascular disease evident as focal neurologic signs or on brain imaging; In the presence of any other physical illness or brain disorder sufficient to account in part, or in total for the clinical picture; or If the parkinsonism only appears for the first time at a stage of severe dementia.

Question 36

DLB vs. Parkinson’s disease Dementia

Answer 36

DLB should be diagnosed when dementia occurs before or concurrently with parkinsonism (if it is present). The term Parkinson’s disease dementia (PDD) should be used to describe dementia that occurs in the context of well-established Parkinson’s disease. In a clinical practice setting, the term that is most appropriate to the clinical situation should be used and generic terms such as LB disease are often helpful. In research studies in which distinction needs to be made between DLB and PDD, the existing one-year rule between the onset of dementia and parkinsonism, DLB continues to be recommended. Adoption of other time periods will simply confound the data pooling or comparison between studies. In other research settings that may include clinicopathologic studies and clinical trials, both clinical phenotypes may be considered collectively under categories such as LB disease or alpha-synucleinopathy.

Question 37

Neuropsychology of Lewy Body Disease

Answer 37

Impairment in basic attention, visual perception, visual construction and memory distinguish LBD from normal aging

impaired visual construction and attention plus relatively spared memory and naming skills can distinguish dementia due to DLB from AD

visual perceptual and attentional impairment relative to memory impairment helps identify dementia due to LBD. In early typical AD, memory impairments are far more pronounced than attention or visual perception problems, but in LBD, attention and visual perception impairments are more salient.

significant deficits in higher order visual processing, a finding that is not attributable to motor slowness associated with parkinsonism. Interestingly, people with LBD who experience visual hallucinations tend to do more poorly on visual tasks

visual problem solving may be negatively affected by executive difficulties in AD, and by perceptual difficulties in DLB.

Memory difficulties, when present in early DLB, appear to be fairly mild and stand in direct contrast to the pronounced amnestic disturbance of AD. The memory problems are more likely to show a pattern of poor initial learning without the rapid forgetting that is typically observed in AD

When people with pure AD (i.e., without concomitant Lewy bodies) were compared to those with pure LBD or mixed AD and LBD, they performed worse on tasks of verbal memory, while patients with pure LBD pathology performed worse on tasks of visual spatial skills.

Question 38

Fronto-temporal Lobar Degeneration

Answer 38

FTLD nosologies include different ranges of diagnoses (e.g., Pick’s disease or primary progressive aphasia), syndromes (e.g., dementia with motor neuron disease), and etiologies (e.g., tauopathies vs. TDP-43 proteinopathies)

Three main phenotypes: behavioral variant-FTD (bvFTD), semantic dementia, and primary progressive aphasia (PPA).
.
PPA can be further subdivided into three variants, including
logopenic (lvPPA),
semantic (svPPA) and
agrammatic (agPPA), sometimes referred to as nonfluent progressive aphasia (PNFA).

PPA is classified based on clinical findings, with speech pathologists currently providing the most sensitive diagnostic differentiation.

Recent pathology studies suggest that the svPPA and agPPA variants of PPA are more consistently predictive of FTLD spectrum disorders (i.e., tauopathies, TDP-43) while the lvPPA variant is strongly associated with AD pathology

Question 39

Mild Cognitive Impairment and FTLD - Behavioural Variant

Answer 39

Behavioral variant-FTD implies, the MCI phase of FTD often presents as impairments in “social cognition” with combinations of obsessions, disinhibition, apathy irritability, elation, lack of empathy or egocentrism, and aberrant motor behavior

Question 40

Mild Cognitive Impairment and FTLD - Temporal Variants (PPA)

Answer 40

Early deficits in predominantly language, semantic knowledge or speech
other neurocognitive deficits in the logopenic variant, in particular, may be affected though to a lesser degree than language (Rohrer et al., 2010, Butts et al., 2015).

Most variants of FTLD show some similarities in behavioral disturbances, and significantly increased behavior disturbance when compared to AD patients matched on age and severity

Question 41

Neuropsychology of FTD - Diagnostic Challenges

Answer 41

(a) the diagnostic criteria for FTD have evolved
and
(b) remain confusing because
(c) FTD is rare and sample sizes in descriptive studies are small, leading to variable findings, and
(d) studies tend to lump bvFTD, semantic dementia, and PPA types to increase sample size, and finally,
(e) to compare and contrast within FTLD syndromes and with other dementias, one must equate for severity. This is challenging since severity scales tend to be disease specific. Additionally, because many neuropsychological tests are mediated by language, assessing neurocognitive functioning beyond language in PPA patients can be particularly challenging. Thus, the known neuropsychological profiles associated with specific FTD syndromes are discussed in the rest of this section.

Question 42

FTD variants: Learning and Memory

Answer 42

FTD syndromes all contrast with AD in the relative preservation of memory early in the illness

differing neuropsychological profiles among the three variants of PPA, including impaired learning and complex retention in lvPPA relative to svPPA and agPPA variants

as dementia worsens, all of the FTD variants show worsening memory performance, due not just to deterioration of attention and language skills, but due to eventual disease encroachment on mesial temporal structures. This highlights the notion that neuropsychological tests may have their greatest value in MCI and early dementia states and lose discriminating value as disease worsens.

Question 43

FTD Fluency and Language

• Damage location?
• Differences across types?
  PP apraxia vs. PPAphasia pathology?

Answer 43

More frontal atrophy is associated with greater lexical fluency problems relative to more temporal patterns of atrophy that show greater challenges in naming.

FTLD patients tend to display comparable deficits in semantic (category) and lexical (letter) fluencies whereas selective category fluency deficits commonly occur in AD

also appears to hold for bvFTD cohorts

Speech apraxia involves neurodegenerative syndrome of the superior lateral premotor and supplementary motor area,

primary progressive apraxia of speech is differentiated from primary progressive aphasia that may affect additional frontal, temporal, parietal, and subcortical regions depending upon PPA variant

Question 44

FTD Language Semantic Knowledge

Answer 44

deficits in aspects of language that cause disruption in daily function.

lvPPA patients have problems with confrontation naming, repeating, and comprehending sentences, relatively preserved single word comprehension, with evidence of anomia, slowed rate of verbal expression due to pauses for word retrieval or verbal formulation, and possible phonemic paraphasias

aphasia in svPPA is dominated by anomia, poor word comprehension, and loss of single word and object meaning. Interestingly, the repetition and fluent speech is relatively preserved though the content may lack specificity

Question 45

FTD Executive Function - testing

Vs. AD on tests?

Answer 45

executive function tests, these tests have limited utility in differential diagnosis

FTLD and AD patients cannot be reliably distinguished by Trail Making Test Part B or the Stroop test

This may arise in part from the problem of mixing different FTLD syndromes, as described, but also may reflect that fairly early there is involvement of the frontal lobes in the typical AD process (Braak & Braak, 1997). However, studies also suggest that executive function tests may not be that good at distinguishing FTLD patients from normally aging samples.

Question 46

FTD Visuospatial Skills

Answer 46

tend to be preserved in FTLD syndromes, given the relative sparing of posterior cortices.

Question 47

Strategies to prevent or delay progression from preclinical MCI to dementia

Answer 47

PRIMARY PREVENTION: tend to be preserved in FTLD syndromes, given the relative sparing of posterior cortices.

lifestyle modifications that improve overall health. A population-wide 25% reduction in midlife diabetes, obesity, hypertension, and physical and cognitive inactivity could potentially alleviate 500,000 cases of dementia

enhancement of cognitive reserve or resilience

putatively useful strategies. This method yields improvement on cognitive test scores specific to the strategy instruction, but gains do not typically generalize to other tests or areas of function

overall benefits of physical exercise are extensive, and there is growing evidence that physical exercise is an important factor in maintaining cognitive and cerebral health. For example, in healthy individuals, physical activity has been shown to help maintain healthy brain volume and provide protection against volume loss

higher levels of physical activity is correlated with larger volumes of the hippocampus, a region essential for memory (Erickson et al., 2009), and acts to increase hippocampal volume

SECONDARY PREVENTION

“memory compensation” or techniques focused on using external aids to help compensate for memory loss. Memory notebooks are a form of memory compensation with validated efficacy in TBI patients

multi component interventions for persons with MCI (Rapp, Brenes, & Marsh, 2002). Mayo Clinic investigators, including this chapter’s lead author (GES), have created a program for MCI that includes five components: (a) memory compensation training with a calendar/ journaling tool; (b) Brain Fitness with a well-studied computerized tool (Barnes et al., 2009; Smith et al., 2009); (c) physical fitness; (d) caregiver and patient support groups; and, (e) wellness education. This ten-day, 50-hour program is called Healthy Action to Benefit Independence and Thinking (HABIT). This intervention has had positive impact on self-efficacy and quality of life outcomes for patients and caregivers

Ascertaining depression can be difficult, even in MCI stages, because patients are challenged to reliably report mood over time. In dementia, the patient’s ability to understand concepts like “feeling blue” or “having low self-esteem” also may deteriorate.

Agitated patients often responded well to antidepressant medication in combination with behavioral activation.

Question 48

Behavioural Strategies in Dementia

Answer 48

For agitated behaviours;

(a) skills training for caregivers, (b) education for caregivers, (c) activity planning and environmental redesign, (d) enhancing support for caregivers, and (e) self-care techniques for caregivers, as well as (f) exercise for the patient and (g) collaborative care with a health professional.
- Understanding the etiology of the dementia syndrome Assessing the severity of the illness Recognizing that behavior is a form of communication and it is important to try to understand what is being communicated based by the behavior: Identifying environmental, physical, psychological, or social factors that may be the impetus for behavioral communication
- Managing antecedents, not consequences Using what the dementia “gives”: taking advantage of the key features of the dementia syndrome to enhance contentment. Focusing on activity-based care Avoidance of efforts to create a behavioral vacuum.

Understanding the Etiology of the Dementia Syndrome

Often, patients in care facilities have a generic dementia diagnosis without benefit of evaluation of the etiology of the dementia. Establishing etiology can avoid iatrogenic mistakes like oversedation from antipsychotic medications. Understanding that different behavioral profiles associate with dementia etiologies, (e.g., fully formed visual hallucinations are common early in LBD, but only later in AD) it is possible to more effectively consider whether comorbidi-ties may be present. For example, observing visual hallucinations would raise concern about delirium early in AD, whereas these symptoms would be an expected part of the disorder in early DLB. Or, disrobing might be understood as simple disinhibition in an early FTD, versus communicating the need to use the bathroom in advanced AD. Understanding the nature and extent of the dementia can help provide the context for understanding what behavior may be communicating. In dementia, understanding that new learning is often impossible helps caregivers understand why frequent reorientation is an exercise in futility and may well be agitating to the person with dementia (and her or his caregiver!). Understanding this cognitive deficit can also clarify behaviors that otherwise get mislabeled.

The case of a person with AD forgetting where she placed valuables, like a purse, then assuming she is being robbed re-frames “paranoia” to rather be poor memory and poor reasoning. Likely the most appropriate intervention here is to have caregivers unobtrusively search living quarters for the purse instead of giving psychotropic medication for psychosis. Understanding these patterns facilitates appropriate intervention plans. Helping caregivers understand these patterns aids their adherence to intervention plans.

Assessing the Severity of the Illness:

The severity of dementia may predispose people to different mediators of disruptive behavior. Mild dementia prone to boredom in wrong environment; may wander, try to self-stimulate.

However, standard care center activities can also be overstimulating (i.e., agitating) to persons with severe dementia who can no longer understand verbal explanations, correctly interpret social interaction, or accommodate noise. Completing a simple but formal mental status evaluation can help to determine environmental mediators of disruptive behavior and assess for the appropriate level of activities-based care.

Recognizing Behavior as a Key Form of Communication

Communication is an adaptive means towards need fulfillment. In patients with dementia, as reasoning and language skills are lost, overt behavior will increasingly become a primary form of communication. Just as a preverbal child uses crying as a means of communicating hunger, pain, or fear, patients with dementia may use wandering, calling out, swearing, or other behaviors to communicate pain, anxiety, boredom, loneliness, etc. Even when speech is intact, verbal communication is often limited by difficulties in expressing desired thoughts correctly. The behavior of patients with advanced dementia often represents an attempt to express feelings and needs that cannot be verbalized adequately. These behaviors often represent an attempt to communicate regarding environmental, physical, psychological, or social factors that are distressing to the person with dementia. Calling such behaviors “inappropriate” or “disruptive” ignores the adaptation efforts reflected in that behavior.

Identifying Environmental, Physical, Psychological, and Social Mediators

What does the behaviour represent for the particular person? The same calling out, wandering, restlessness, aggression, and other difficult behaviors might be the expression of an inner emotional state in one patient, a long-standing behavioral pattern in another, an unrecognized physical need in a third patient, and a reaction to an external stimulus in a fourth. If clinicians observe only the behavior itself and ignore the complex mediators that may be at play, intervention is unlikely to be effective.

Environment

evaluating the person in his or her typical living environment when possible. Multiple, simultaneous, or unnecessary stimuli may be difficult for the patient to interpret or may be overwhelming. “Old-fashioned” music may be soothing to the patient, but modern music preferred by the young-adult care provider may be agitating.

Physical Factors

Cut back salt for blood pressure but is it worth it? They hate their food and the environment annoys them.

Social Factors

They retain a need to be sociable. Are they getting that?

Managing Antecedents, Not Consequences

New learning isn’t going to happen. So change what leads to a behaviour.

Using What the Dementia “Gives”

You can use distraction because they are impaired and don’t notice. So use it. Don’t get annoyed. Validate the emotion, collaborate (you want to go home? me too), distraction if there are attention problems.

Focusing on Activity-Based Care

Planned activities should be “failure free,” promoting a sense of success by accommodating the ability level of the patient. Meaningful activities should correspond to individual’s life history, current abilities, and attention span when possible. Exercising existing abilities in a failure-free manner will provide reassurance and contribute to a sense of competence.