1. DEMENTIA NEUROCOGNITIVE DISORDER 2015
37th Annual Family Medicine Intensive Review Course
May 16, 2015
Shelia R. Cassidy, Psy.D.
Asst. Professor & Clinical Neuropsychologist
UAMS College of Medicing
Reynolds Institute on Aging

2. Disclosures
The following speaker of this CME activity has no relevant financial relationships with commercial interests to disclose:
SHELIA R. CASSIDY, PSYD

3. OBJECTIVES Alzheimer’s disease Vascular dementia Lewy Body dementia
Differentiate 4 MOST COMMON types of dementia syndromes through functional clinical presentations.
Alzheimer’s disease
Vascular dementia
Lewy Body dementia
Frontotemporal dementia
2. Discriminate neuropsychiatric conditions associated
with dementia syndromes.
Dementia aka Major Neurocognitive Disorder most frequently manifests as progressive mental impairment that accompany any of several disease processes of the brain and nervous system. Symptoms can include forgetfulness, personality changes, movement problems and mood changes. One of the key concerns of older adults is the experience of memory loss that is qualitatively different from normal aging. Occasional lapses in memory are normal in aging adults but understanding the distinction between normal age-related cognitive changes and warning signs of Neurocognitive disorders are critical to maximizing cognitive health.
At present, definitive diagnosis can only be determined by brain biopsy or after death by autopsy. Recent emphasis has been toward finding a combination of biomarkers that delineate differential diagnosis.
Several different forms of dementia exist, with four of the most common including Alzheimer’s disease, Lewy body dementias, vascular dementia and fronto-temporal dementias. Although prevalence of Alzheimer’s disease can be difficult to calculate due to suspected under-recognition of many cases, this condition is more prevalent in people over the age of 60. Alzheimer’s disease is the most common type of major neurocognitive disorder affecting about 5 million Americans. Alzheimer's pathology includes the development of plaques, specifically deposits of amyloid peptide, in the brain as well as neurofibrillatory tangles, which are clusters of proteins found in dead brain cells.  Lewy body dementias affect 1.3 million Americans and their families, according to the Lewy Body Dementia Association. This umbrella term includes both Parkinson’s disease dementia and dementia with Lewy bodies. Lewy bodies are proteins found in the brain stem that deplete the neurotransmitter dopamine, which in turn affects movement resulting in Parkinsonian symptoms. In Lewy body dementia, these proteins diffuse throughout the brain, including the cortex. This results also in the depletion of the neurotransmitter acetylcholine, which causes behavior, thinking and perception disturbances.
Vascular dementia occurs as a result of problems with the brains blood vessels due to narrowing or obstructive blockage causing disruption of blood flow and ischemic tissue damage. Transient ischemic
Attacks are caused by temporary blockage from a clot. TIA symptoms (confusion, dysarthric speech, lateralized weakness occur rapidly and last a relatively short time. Most TIAs last less than five minutes; the average is about a minute. When a TIA is over, it usually causes no permanent injury to the brain. However, patients may sustain multiple silent ischemic events in the deep periventricular, globus pallidus, and corona radiatta deep white m white
the brain.
, as in a stroke, or the blood vessels may narrow obstructing oxygenation of the brain. Multiple infarct dementia can be caused by several mini-strokes in the brain. These blood vessel problems Frontotemporal Dementia
Frontotemporal dementia, or FTD, serves as an umbrella term for several brain disorders that affect the frontal and temporal lobes of the brain. It used to be known as Pick’s disease, which now indicates a specific subtype of the disorder. The causes of FTD remain largely unknown. In FTD, the frontal and temporal lobes begin to shrink due to loss of neurons, leading to behavioral changes, speech and language problems and movement disorders. FTD tends to occur earlier than Alzheimer’s, between the ages of 40 and 70. No cure or effective treatment exists.

4. Normal Aging Structural BRAIN Changes CHEMICAL BRAIN CHANGES
Thinning of the Cortical Gray Matter
Age-Related changes in Neuronal Morphology
Oxidative Stress
DNA Damage
Less efficient Neural Circuits and Brain Plasticity
CHEMICAL BRAIN CHANGES
Dopamine
Serotonin
Glutamate
GENETIC CHANGES
Decline in Gene expression functions
Normal aging is associated with a decline in various memory abilities comprising many cognitive tasks; the phenomenon is known as age-related or age associated memory impairment (AAMI). The ability to encode new memories of events or facts and working memory shows decline in both cross-sectional and longitudinal studies.[8] Studies comparing the effects of aging on episodic memory, semantic memory, short-term memory and priming find that episodic memory is especially impaired in normal aging; some types of short-term memory are also impaired.[9] The deficits may be related to impairments seen in the ability to refresh recently processed information.

5. Normal Age-Related Cognitive Changes
INTACT FUNCTIONING
Sensory Motor
Visual Spatial
Receptive & Expressive Language
Memory for personal history & recent events
Executive – Intelligence, fund of information, math skills, judgment, decisional capacity
IADLs
SLIGHT DECLINES Attention/Concentration
Processing speed slowing
Word finding
“Tip of the Tongue”
Memory “senior moments”
Executive abstract reasoning
Compensatory strategies
Activation of specific brain areas (mostly the hippocampus) seems to be different between younger and older people upon episodic memory retrieval.[16] Older people tend to activate both left and right hippocampus, while younger people activate only the left one. 

6. Risk factors for ABNORMAL cognitive decline
Increasing Age
Hypertension
Cardiac disease
Diabetes
Poor nutrition
Social isolation
Family history of dementia
Psychological factors: stress & depression

7. Stages of Assessment with pt & informant 2. Physical & Neuroexam
Stage One
1. Medical & psychocial hx
with pt & informant
2. Physical & Neuroexam
3. Mood & behavioral screening –
SIGECAPS & Anxiety
4. Cognitive Screening- MMSE,
MoCA, SLUMS, etc. Make sure
vision, hearing, or accents are
NOT lowering score
Stage Two
Labs – CBC, Chem 7, Liver fx, Thyroid, Metals, Vit B-12, D-3, serological test as indicated, etc.
Stage Two (cont.)
Neuroimaging – dependent on findings of H & P – if over 75 & consistent with AD may not meet medical necessity
Stage Three
Treat potentially reversible conditions, medications, mood, sleep apnea, B-12 deficiency, etc.
Stage Four
Rescreen cognition after tx & if still abnormal – refer for Neuropsych eval
Assess effort if secondary monetary gain is present – such as disability or civil suits are present (more likely in younger patients)

9. Neurocognitive Disorder Etiology
Disease TYPE
Neurocognitive Disorder Etiology
Parenchymal Brain
Disease
Alzheimer’s disease, Parkinson’s disease, Huntington’s Chorea, Progressive Supranuclear Palsy
Vascular Neurocognitive
Disorder
Multi-Infarct, Focal Infarct, Subcortical Ischemic Vascular Dementia (Binswanger disease)
Neurocognitive Disorder due
to med side effects,
substance abuse, or toxins
Alcohol, drugs, heavy metals, Bromide, CO, Benzodiazepines, Psychotropics (ie, antipsychotics, opiates, sedatives, etc.) (toxin exposure/drugs)
Neurocognitive Disorder
due to metabolic dysfx
Chronic hepatic/uremic encephalopathy, dialysis, Wilson’s disease (metabolic dysfunction)
to Endocrine disorders
Pituitary, Parathyroisis, Thyroid, Adrenal dysfunction
to nutritional deficiencies
Pernicious anemia, Pellagra, Folic Acid, Thiamine
due to Infectious dissease
HIV/AIDS, Neurosyphyllis, Chronic Meningitis, Creudtzfeldt Jacob disease (Infectious disease)
Increased Intracranial
Pressure
Brain tumor, Head Trauma, Hematoma, Hydrocephalus

10. DELIRIUM Mild or Major NCD Onset Acute to Sub-acute Insidious Course
Fluctuating
Stable and Progressive
Duration
Hours to day (rarely weeks)
Months to years
Attention
Fluctuates
Steady
Sensorium
Often impaired – can fluctuate rapidly
Clear until later stages
Etiology
Usually immediate cause identified
Usually no immediate cause
Psychomotor activity
Increased, decreased, or unpredictable
Can be normal
Cognitive function
Globally impaired, poor attn span
Poor short-term memory, attn span less affected
Perception
Visual hallucinations, fleeting common delusions
Simple delusions & hallucinations
Sleep/wake cycle
Disrupted, reversed Sun downing
Sun downing
Manepali, et al. Primary Psychiatry. Vol 14, No. 8, 2007

11. DEPRESSION NCD – Alzheimer’s Onset Rapid Insidious Duration Short Long
Mood
Diurnal variation, usually depressed
Fluctuating from apathy to normal to irritability
Intellectual fx
Impaired; answers “I don’t know”
Impaired; answers questions incorrectly; minimizes or rationalizes errors
Memory Loss
Recent and remote answers
Recent most affected
Self Image
Poor
Normal
Associated Sx
Anxiety, insomnia, anorexia
Rare, occasional insomnia or uncooperative
Consultation reason
Self-referral
Family referral
Previous History
Previous depression, social problems
Family hx of dementia

12. RECENT TERMINOLOGY CHANGES
DSM-IV
Mild Cognitive Impairment
DSM-5
Mild Neurocognitive Disorder
DSM-IV
Dementia due to …
DSM-5
ICD-9/1CD-10 +
Major Neurocognitive Disorder

13. DSM-5 Pertinent Cognitive Domains
Complex attention Executive function Learning and memory Language Perceptual Motor Social cognition

14. Normal Aging vs. Progressive dementia
Mild NCD
Major
NCD

15. Mild Neurocognitive Disorder Major Neurocognitive Disorder
AGING VS DISEASE CONTINUUM
Normal Aging
Mild Neurocognitive Disorder
Major Neurocognitive Disorder
Decline from lifelong abilities in 1 or more areas of thinking + inefficiency in daily activities
Needs help with daily activities + substantial decline in 1 or more cognitive abilities
Primarily
intact cognition, subtle processing speed slowing & less efficient attention & executive reasoning

16. Functional/Clinical Decline
DAILY FUNCTIONING
BASIC transfers, ambulation, bathing, hygiene, & feeding
INSTRUMENTAL ACTIVITIES
Safe use of appliances
Phone answering & dialing
Laundry
Housekeeping
Meal Preparation
Shopping
Management of finances
Management of meds
Driving
COGNITIVE DOMAINS
General Intelligence
Sensory Motor
Attention/Concentration
Processing Speed
Visual Spatial Functions
Language Functions
Memory – Auditory & Visual
Executive – higher thinking & reasoning
MOOD & BEHAVIORS

17. DSM-5 Mild Neurocognitive Disorder
Evidence of modest cognitive decline from premorbid fx in 1 or more cognitive domains based on:
Concern of pt OR a knowledgeable informant, OR the clinician that there has been a mild decline in cognitive fx +
ModestLY impaired cognitive performance on standardized neuropsychological testing or, in its absence, another quantified clinical assessment.
Cognitive deficits do NOT affect independence in IADLs, but may require greater effort or compensatory strategies.
The cognitive deficits do not occur exclusively in the context of a delirium & are NOT better explained by another mental disorder (e.g., major depressive disorder, schizophrenia).

18. DSM-5 Major Neurocognitive Disorder
A. Evidence of significant cognitive decline from previous abilities in one or more cognitive domains based on:
1. Concern of pt OR a knowledgeable informant OR clinician that there has been a significant decline in cognitive function; AND
2. Substantially impaired cognitive performance on standardized neuropsychological testing or, in its absence , another quantified clinical assessment.
B. Cognitive deficits interfere with independence in activities.
Cognitive deficits not due exclusively to a delirium.
D. Cognitive deficits not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia).

19. Major NCD Specify: 1. Without behavioral disturbances
2. With behavioral disturbances: if cognitive disturbance
plus a clinically significant behavioral disturbance
psychosis, mood disturbance, agitation, or apathy.
1. Mild: difficulties limited to IADLs
2. Moderate: difficulties with basic activities of daily living
3. Severe: fully dependent

20. Vascular Neuro-cognitive
Disorder due to
Alzheimer’s
disease
OTHERS:
Parkinson’s
Depression
Seizures
NPH
Trauma
Infection
Metabolic
Drugs/Toxins
Neoplasms
Anoxia
Vascular Neuro-cognitive
Disorder
Neuro-cognitive disorder with Lewy Bodies
Fronto-Temporal Neuro-Cognitive
Disorder

21. PROPORTIONAL RANGE OF DEMENTIA SUBTYPES

22. “Alzheimer’s disease is bankrupting America”
AD – 6th-leading cause of death in US. AD - only disease in top 10 causes of death in America without a way to prevent it, cure it or significantly slow its progression. Currently $172 billion is spent caring for people with AD & other dementias. By 2050, the costs may reach over $1 trillion without adjusting for inflation. Almost 1/2 of all AD costs are paid by Medicare & more than one in every six Medicare dollars is spent on a pt with AD Between 2010 & 2050, Medicare costs Medicare of caring for a pt with AD will increase over 600 % & out of pocket costs to families will grow more than 400 %.

23. Ten Key Warning Signs for AD
Alzheimer’s Assoc. AD10:
Memory loss
Difficulty performing familiar tasks
Problems with language
Disorientation to time and place
Poor or decreased judgment
AD10 (continued):
Problems with abstract thought
Misplacing things
Changes in mood or behavior
Changes in personality
Loss of initiative

24. Alzheimer’s disease facts and figures
5.3 million Americans have AD million are aged 65 and over (1 in 8). By 2050, 13.5 to 16 million in US will have AD Nearly 1 in 2 aged 85 and over has the disease. Every 70 seconds, someone in US develops Alzheimer’s. In 2050, every 33 secs an American will develop AD Survival is an average of 4 to 8 years after diagnosis with AD, but many live for as long as 20 years with the disease. On average, 40 % of person’s years with AD are in the most severe stage of the disease.

25. AGE IS HIGHEST RISK FACTOR FOR AD
(Weuve et al 2012
AGE IS HIGHEST RISK FACTOR FOR AD
Age 30 – 65
Early Onset
10% of total AD pts – some autosomal dominant mutation in
Amyloid precursor protein, presenilin 1 or presenilin 2
Age 65 – 74
7% of total AD pts –
Age 75 – 84
43% of total AD pts
Age 85 & up
40% of AD pts
Total AD pts
100% - Female:Male = 2:1 ratio
Genetics
Familial 5 to 15% of cases;
APOE4  risk factor NOT dx marker – not necessary for AD
Susceptibility - polymorphism APOE-4 & earlier onset in
homozygous individuals.
Down’s syndrome (trisomy 21 gene) AD if survive to midlife
Risk Factor /
Disease
Course
Vascular risk factors AD by cerebrovascular pathology or thru direct effects on AD pathology
Typical course 8 to 10 yrs after dx, but some live 20 years
Late stage AD become mute and bed bound
Early onset more likely to survive full course
Late onset dx more complex multiple comorbidities
Death commonly due to aspiration
ALZHEIMER’S DISEASE

26. MILD NCD due to Alzheimer’s Disease
A. Criteria met for MILD neurocognitive disorder.
B. Insidious onset & gradual progressive impairment in 1 or
more cognitive domains.
C. Not interfering with IADLs but more difficult & use
compensatory strategies.
1. May or may NOT have evidence of a causative AD genetic
mutation from family history or genetic testing, BUT
2. All 3 of the following are present:
a. Clear evidence of decline in memory & learning + at least
1 other cognitive domain (detailed history or serial
neuropsychological testing).
b. Steadily progressive, gradual decline in cognition, without
extended plateaus.
c. No evidence of mixed etiology

27. DSM 5 MAJOR NCD due to Alzheimer’s disease
A. Criteria met for MAJOR NCD.
B. Insidious onset & gradual progressive impairment in 2 or more
cognitive domains.
POSSIBLE AD if only one of the following are present 
Probable AD if either of the following is present 
Interferes with IADLs fx
The following CRITERIA are also met:
a. Clear evidence of decline in memory & learning + at least 1
other cognitive domain (based on detailed history or serial
neuropsychological testing).
b. Gradual progressive decline in cognition w/o long plateaus.
c. NO evidence of MIXED etiology

28. Neuropsychiatric Features AD
~ 80% of pt with MAJOR NCD due to Alzheimer’s disease  behavioral & psychological SX – that are also frequent at the MILD stage.
Behavioral symptoms = or more distressing than cognitive SX & are frequently the reason health care is sought.
Mild Stage NCD due to AD  depression & apathy
Moderate Stage NCD due to AD  psychotic features, irritability, agitation, combativeness, sundowning & wandering
Rummaging, hiding, & hoarding
Delusions: Paranoia & persecutory themes
Late Stage NCD due to AD  gait disturbance, dysphagia, incontinence, myoclonus, and seizures

29. Neurofibrillary Tangle
Amyloid Plaque

30. http://www. drugdevelopment-technology

31. Biomarkers in the Game Invasive, time consuming, & expensive
Structural & functional magnetic resonance imaging
Cerebrospinal fluid tau and amyloid-β levels
Pittsburg compound amyloid imaging or “inflammaging”
Blood based biomarkers will likely become more pragmatic
Mark Mapstone, Howard Federoff et Georgetown University
525 people aged 70 & over for 5 years.
74 developed aMCI or mild AD
46 of the 74 were incidental cases
28 of 74 (the "converters") converted from nonimpaired memory status at entry to aMCI or AD, over an average time of 2.1 years.
Validated set of 10 peripheral blood lipids that predicted phenoconversion to either amnestic MCI or AD within a 2–3 year timeframe with a sensitivity and specificity of 90% accuracy

32. NCD pharmacological treatment for AD
Acetylcholinesterase Inhibitors
donepezil (Aricept)
rivastigmine (Exelon)
galantamine (Razadyne)
tacrine (Cognex) – less used due to side effects
memantine (Namenda) – NMDA antagonist

33. Vascular Neurocognitive Disorder
2nd most common cause of dementia in elders Potentially preventable condition/slow progression  tight BP & BG control (90 – 150 mg/dL) + cholesterol lowering therapy Highest 5-year mortality rate (61%) of all dementias TYPES: 1. CADASIL (Cerebral autosomal dominant arteriopathy with leukoencephyalopathy) gene mutation Notch 3 2. Multi-Infarct Dementia 3. Subcortical Ischemic Vascular Dementia (SIVD)
Beers MH, Porter RS, Jones TV, et al. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:1635,1727, ,
What is Dementia? National Institute of Neurological Disorders and Stroke. National Institutes of Health. Available at: Accessed March 31, 2015

34. Vascular NCD  

35. Major or Mild Vascular Neurocognitive Disorder
Criteria are met for major or mild NCD Clinical features are consistent with a vascular etiology, as suggested by the following: Onset of cognitive deficits is temporally related to 1 or more cerebrovascular events Evidence for decline is prominent in complex attention (including processing speed) and frontal-executive function. There is evidence of the presence of cerebrovascular disease from history, physical examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits. The symptoms are not better explained by another brain disease or systemic disorder.

36. Possible vs. Probable Vascular NCD
Possible vascular NCD  symptoms meet clinical criteria but NO neuroimaging + temporal relationship of the neurocognitive syndrome with 1 or more cerebrovascular events is not established. Probable vascular NCD is diagnosed if 1 of the following is present Clinical criteria supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported). The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events. Both clinical & genetic (CADASIL) evidence of cerebrovascular disease is present.

37. Neuropsychiatric features of Vascular Neurocognitive Impairment
Personality change
Apathy / Dependent behaviors / lack of insight
Impaired social communication with family and friends
Mistrust
Repetitive fixated behaviors
Neglect of hygiene & appearance
Guilt or shame
Generalized Anxiety
Frequently Depressed
Agitation /Anger /Disrespectful
Increased risk of self harm – impulsivity, dangerous risk-taking
When severe, may have delusions, hallucinations, delirium

38. Neurocognitive Disorder due to Lewy Bodies
Criteria are met for major or mild NCD.
Insidious onset & gradual progression.
Combination of CORE dx features & suggestive dx features for either probable or possible NCD with Lewy bodies.
probable major or mild NCD with Lewy bodies, the individual has 2 core features, or 1 suggestive feature with 1 or more core features.
possible major or mild NCD with Lewy bodies, the individual has only 1 core feature, or 1 or more suggestive features.
CORE diagnostic features:
Fluctuating cognition with pronounced variations in attention & alertness.
Recurrent visual hallucinations that are well formed and detailed.
Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline.
Suggestive diagnostic features:
Meets criteria for rapid eye movement sleep behavior disorder
Severe neuroleptic sensitivity
Disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

39. Lewy Body Pathology Braak & collegues – staging system in
PD applied to LB
Stage 1: pathology in dorsal motor
nucleus of CN 9/10 & intermediate
reticular zone of medulla
Subsequent LB ascension thru pons, midbrain, & subcortical structures to finally the neocortix in stages 5 & 6
Susceptible – olfactory bulb, dorsal motor nucleus of vagal nerve, other brainstem structures & PNSincluding enteric nervous system
Actual amount of LB pathology does NOT correlate with symptom severity
Donaghy and McKeith The Clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis Alzheimer's Research & Therapy 2014, 6:46

40. Lewy Body Pathology (cont.)
DLB & PDD pathological differences - DLB - higher amyloid plaque deposition in the striatum
More αSyn deposition in CA2/3 area of hippocampus & higher frontal cortical 5-HT1A receptor density
DLB less cell loss - substantia nigra & minimal D2 receptor up-regulation in striatum
Coexisting LB & AD pathology (amyloid-beta (Aβ) and tau) postmortem
DLB < structural brain changes compared with AD

41. Mild or Major Neurocognitive Disorder With Lewy Bodies
Affects 2ce as many men Fluctuations in alertness, attention, & cognition Decline in smell (hyposmia) Postural Dizziness Constipation Parkinsonian symptoms - muscles that go abnormally rigid or tremble uncontrollably Relative preservation of short-term memory unlike AD Later in course - memory loss, poor judgment, and confusion .

42. Supportive features of NCD due to Lewy Bodies
Repeated Falls & Syncope
Transient unexplained loss of consciousness
Severe autonomic dysfunction (orthostatic hypotension, incontinence)
Relative preservation of medial temporal structures on CT or MRI
Generalized low uptake on PET / SPECT perfusion scan with reduced occipital activity
Abnormal low uptake on MIBG myocardial scintigraphy
Prominent slow wave activity on EEG with transient temporal lobe sharp waves

43. Neuropsychiatric features of NCD due to Lewy Bodies
Rapid Eye Movement (REM) sleep d/o – parasomnia characterized by enactment of dreams (kicking, punching) that often results in injury Systematized Delusional thinking Ego Syntonic well formed visual hallucinations Hallucinations in other modalities Depression – ¼ pts Anxiety – ¼ pts

44. Frontotemporal Neurocognitive Disorder (FTNCD)
Criteria met for major or mild neurocognitive disorder
Disturbance - insidious onset and gradual progression
Either (1) or (2):
Behavioral variant:
3 or more of the following behavioral symptoms:
Behavioral disinhibition
Apathy or inertia
Loss of sympathy or empathy
Perseverative, stereotyped or compulsive/ritualistic behavior
Hyperorality and dietary changes
Prominent decline in social cognition and/or executive abilities.
Language variant:
Prominent decline in language ability, speech production, word finding, object naming, grammar, or word comprehension
Relative sparing of learning and memory & perceptual-motor function.

45. Frontotemporal NCD (cont.)
The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.
Probable frontotemporal neurocognitive disorder is diagnosed if either of the following is present:
Evidence of a causative Frontotemporal neurocognitive disorder genetic mutation, from family history or genetic testing.
Evidence of disproportionate frontal and/or temporal lobe involvement on neuroimaging.
Possible frontotemporal neurocognitive disorder is dx’d if:
NO evidence of a genetic mutation
NO neuroimaging has not been performed.

46. Progressive Supranuclear Palsy (PSP)
VARIANTS
Frontotemporal NCD
Behavioral
Variant (bvFTNCD)
Language
Variant (lvFTNCD)
Motor Neuron Disease
Picks Complex
Progressive
Nonfluent Aphasia
Semantic Dementia
Progressive Supranuclear Palsy (PSP)
Corticobasal
Degeneration (CBD)

47. BEHAVIORAL VARIANT Frontotemporal Neurocognitive Disorder
60 % of FTNCD pts have (bvFTNCD) Dysfunction in frontal & temporal lobes Diminished social skills, emotional regulation, personal conduct, & self awareness Mood changes – stubbornness, emotinal coldness or distance, apathy, & selfishness Initially limited confusion about place or time

48. FTNCD (cont.)
Inability to control impulsive urges /impulsive behavior Poor decision-making Loss of the ability to empathize with others Decrease in personal motivation Changes in grooming or eating habits Language- or speech difficulties – aphasia or dysarthria Loss of the ability to use words that make sense for a given conversational context Less frequently FTNCD – impaired body movement Rigid or trembling & weak muscles Loss of the ability to coordinate the activity of different muscles Swallowing problems.

49. Frontotemporal Neurocognitive Disorder Language Variant PROGRESSIVE NONFLUENT APHASIA (PNFA)
20% of FT NCD cases – temporal lobe dysfunction Receptive language deficits – difficulty understanding complex sentences. Expressive language deficits - difficulty producing language fluently though they still know the meaning of the words they are trying to say; talk slowly, have trouble saying words, difficulty talking in groups of people or on the telephone Eventually, many pts with PNFA develop severe Parkinsonian symptoms overlapping with Progressive Supranuclear Palsy (PSP) & Corticobasal degeneration (CBD) – inability to move eyes side-to-side, muscle rigidity in arms & legs, falls, & weakness of muscles around the throat.
Primary progressive aphasia (PPA) causes a person to have trouble with expressive and receptive speaking—finding and/or expressing thoughts and/or words. Sometimes a person with PPA cannot name common objects. Problems with memory, reasoning, and judgment are not apparent at first but can develop and progress over time. PPA is a language disorder not to be confused with the aphasia that can result from a stroke. Many people with PPA, though not all, develop symptoms of dementia. PNFA accounts for only about 20% of all people with FTD. Unlike semantic dementia where the person maintains the ability to speak but loses the meaning of the word, people with PNFA have difficulty producing language fluently even though they still know the meaning of the words they are trying to say. The person may talk slowly, having trouble saying the words, and have great trouble with the telephone, talking within groups of people or understanding complex sentences. In recent years it has become apparent that many patients with PNFA go on to develop severe Parkinsonian symptoms that overlap with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) such as an inability to move the eyes side-to-side, muscle rigidity in the arms and legs, falls, and weakness in the muscles around the throat.
Major or mild frontotemporal neurocognitive disorder (NCD) comprises a number of syndromic variants characterized by the progressive development of behavioral and personality change and/or language impairment. The behavioral variant and three language variants (semantic, agrammatic/nonfluent, and logopenic) exhibit distinct patterns of brain atrophy and some distinctive neuropathology. The criteria must be met for either the behavioral or the language variant to make the diagnosis, but many individuals present with features of both.
Individuals with behavioral-variant major or mild frontotemporal NCD present with varying degrees of apathy or disinhibition(Rascovsky et al. 2011). They may lose interest in socialization, self-care, and personal responsibilities, or display socially inappropriate behaviors. Insight is usually impaired, and this often delays medical consultation. The first referral is often to a psychiatrist. Individuals may develop changes in social style, and in religious and political beliefs, with repetitive movements, hoarding, changes in eating behavior, and hyperorality(Rabinovici and Miller 2010). In later stages, loss of sphincter control may occur. Cognitive decline is less prominent, and formal testing may show relatively few deficits in the early stages. Common neurocognitive symptoms are lack of planning and organization, distractibility, and poor judgment. Deficits in executive function, such as poor performance on tests of mental flexibility, abstract reasoning, and response inhibition, are present, but learning and memory are relatively spared, and perceptual-motor abilities are almost always preserved in the early stages.
Individuals with language-variant major or mild frontotemporal NCD present with primary progressive aphasia with gradual onset(Mesulam 1987), with three subtypes commonly described: semantic variant, agrammatic/nonfluent variant, and logopenic variant(Gorno-Tempini et al. 2011; Josephs 2008), and each variant has distinctive features and corresponding neuropathology.
“Probable” is distinguished from “possible” frontotemporal NCD by the presence of causative genetic factors (e.g., mutations in the gene coding for microtubule-associated protein tau) or by the presence of distinctive atrophy or reduced activity in frontotemporal regions on structural or functional imaging.
Associated Features Supporting Diagnosis
Extrapyramidal features may be prominent in some cases, with an overlap with syndromes such as progressive supranuclear palsy and corticobasal degeneration. Features of motor neuron disease may be present in some cases (e.g., muscle atrophy, weakness). A subset of individuals develop visual hallucinations.

50. FT NCD SEMANTIC DEMENTIA (SD)
20 % of FTD cases – Temporal lobe dysfunction
Left Hemispheric onset – loss of meaning for words, decline in reading & spelling, decline in people’s names; Memory not affected until later; intact orientation to place & time, intact muscle control
Right Hemispheric onset – trouble recalling faces of friends & familiar people; deficits understanding emotions of others; loss of empathy
Eventually both hemispheres will become dysfunctional
SD patients eventually develop behavioral problems – disinhibition, apathy, diminished insight
Semantic dementia, which has also been called "temporal variant FTD," accounts for 20% of FTD cases. Language difficulty, the predominant complaint of people with SD, is due to the disease damaging the left temporal lobe, an area critical for assigning meaning to words. The language deficit is not in producing speech but is a loss of the meaning, or semantics, of words. In semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.
For example, early in the illness a patient might lose the word for a falcon, later-on forget the word for a chicken, then call all winged creatures "bird" and eventually call all animals "things." Not only do they lose the ability to recall the word, but the concept of these words is also lost. "What is a bird?" might be a typical response for a patient with advanced SD. Reading and spelling usually decline as well, but the person may still be able to do arithmetic and use numbers, shapes or colors well. Names of people, even good friends, can become quite difficult for people with SD. Like the behavioral variant, memory, an understanding of where they are, and sense of day and time tend to function as before. Muscle control for daily life and activities tends to remain good until late in the disease. Some of these skills may seem worse than they actually are because of the language difficulty people with SD have when they try to express themselves. When SD starts in the right temporal lobe, people in the early stages have more trouble remembering the faces of friends and familiar people. Additionally, these people show profound deficits in understanding the emotions of others. The loss of empathy is an early, and often initial, symptom of patients  with this right-sided form of SD. Eventually people with right-sided onset progress to the left side and then develop the classical language features of SD. Similarly, left-sided cases progress to involve the right temporal lobe and then the person experiences difficulty recognizing faces, foods, animals and emotion. SD patients eventually develop classical bvFTD behaviors including disinhibition, apathy, loss of empathy and diminished insight. The time from diagnosis to the end is longer than for those with bvFTD, typically taking about six years.

51. FT NCD with Motor Neuron Disease
15 % of pts with FTNCD also develop motor neuron disease (FTNCD-MND) MND affects motor nerve cells in spinal cord, brain stem, and cerebral cortex Motor sx = tremors, jerks (chorea or myoclonus), excessive startle response, seizures More frequently found in pts with bvFTNCD Rare in SD or PNFA Most common MND is amyotrophic lateral sclerosis (ALS). Often pts with ALS have behavioral or cognitive problems similar to those seen in FTNCD. MND Symptoms: slurring of speech, difficulty swallowing, choking, limb weakness, or muscle wasting. Often a family history of the disease

52. Neuropsychiatric features of FTNCD
Inattention Low Motivation, Apathy or inertia Poor Insight Behavioral disinhibition Aggression Impulsivity Sexual Impropriety Loss of sympathy or empathy Perseverative, stereotyped or compulsive behavior Hyperorality and dietary changes

53. Mild Neurocognitive Disorder
Mild or Major Neurocognitive Disorder
Mild Neurocognitive Disorder
Potentially Reversible Causes
Subjective cognitive complaint corroborated by informant Objective cognitive impairment, preserved general cognition INTACT IADLs
Depression, drug side effects, metabolic d/os, vitamin deficiency, infectious disease, neoplams NPH, subdural hematoma
Gradual onset,
progressive decline,
ADL deficits,
memory loss,
aphasia, apraxia,
agnosia, executive
dysfunction
Acute onset,
stepwise decline, vascular risks, frontal deficits, neurological signs, neuroimaging findings
Hallucinations,
parkinsonism,
attn / arousal fluctuations, executive dysfx,
visuospatial deficits
Early onset, family
history, executive
dysfx, disinhibition, personality change, aphasia (fluent /
non-fluent
Dementia of the Alzheimer’s Type
Vascular Dementia,
Fronto-Temporal Dementia
(NINCDS-ADRDA, NINDS-AIREN, Hackinski Ischemia Scale, DSM-IV-TR, Neary Consensus Criteria), and making use of instruments such as the Folstein Mini-Mental Status Exam (MMSE; Folstein et al., 1975) make defining dementia type and severity possible
mNCD AD
NCD LB or PD
bvFTNCD
lvFTNCD
Vascular NCD

54. PREVENTION & NONPHARMACOLOGICAL TREATMENT
Controlling risk factors for chronic disease, such as heart disease and diabetes (e.g., tight control of blood cholesterol and blood pressure at healthy levels & maintaining a healthy weight)
Enjoying Consistent exercise regimen and physical activity
Reduce stress – limit caffeine, meditation routine &/or mindfulness
Eating a healthy lifestyle diet - including plenty of vegetables & fruits, such as the Mediterranean diet
Engage in intellectually stimulating activities and maintaining close social ties with family, friends, and community
Don’t smoke & Limit alcohol intake
Get 7 to 9 hours of sleep each night
Do activities that require quick responses – ping pong, tennis, board games, computer games

55. Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)
2,802 healthy adults ages 65 & up living independently – 4 10 computer sessions
Memory  26% improved
Reasoning  74% improved
Processing Speed  87% improved
Control group
11 mos later 60% 75-minute “booster” sessions
5 years later Groups > controls
REASONING & PROCESSING SPEED groups

56. Any Questions?
Thank you!