Non Alzheimer’s Dementia Kevin Overbeck, DO Assistant Professor UMDNJ –SOM NJISA The science of diagnosing dementia has progressed to the point that patients can be accurately characterized before autopsy. Clinic management of dementia (+ evolving symptoms) as well as education of the family/caregiver(s), enables the patient to remain in the home as long as it is safe for all concerned. This support and education improves the quality of life of the patient and family. True degenerative dementia means that a particular disease entity is continuously destroying neurons (or neuronal connections). When enough neurons have been killed, the brain is visibly atrophied, as seen on MRI scans, and/or demonstrates reduced metabolic activity levels in certain areas, as seen in PET scans. At some point, the patient’s behavior changes; family members are almost always the ones who notice these initial changes so it is important to partner with them.

Non-Alzheimer’s Dementia This medical student presentation is offered by the New Jersey Institute for Successful Aging. This lecture series is supported by an educational grant from the Donald W. Reynolds Foundation Aging and Quality of Life program.

Learning Objectives Compare and contrast clinical features that distinguish vascular dementia, frontotemporal dementia, and Lewy body dementia Differentiate between Alzheimer's disease and all other dementias

Prevalence of Common Dementias Relative Prevalence of Common Dementias FT = Frontotemporal dementia “Other” includes normal pressure hydrocephalus, HIV-related dementia, Creutzfeldt-Jakob disease, Huntington’s disease The most well-know dementia is Alzheimer’s disease (AD). In the past, 70-80% of patients were diagnosed with this disease, but now it accounts for approximately 50% of cases. Here are the relative frequencies of dementias in the elderly. Keep in mind that there can be overlap perhaps referred to as a “mixed type” of dementia. For example, Alzheimer’s disease and vascular dementia can occur in the same person. Parkinson’s dementia (1-3%) – There is ongoing controversy regarding Parkinson’s dementia. What about alcoholic dementia prevalence? Reference: Image Source: Weiss BD. Elder Care: A Resource for Interprofessional providers. http://aging.medicine.arizona.edu Accessed: October 5, 2011. Image Source: Weiss BD. Elder Care: A Resource for Interprofessional providers. http://aging.medicine.arizona.edu Accessed: October 5, 2011.

Evaluation of Memory Loss HPI (establish timeline and clinical presenting features) Detailed MED review CAM GDS MMSE/CDT Pertinent physical exam findings LABs (BMP, CBC, LFTs, TSH, B12, Folate) Brain imaging (CT Scan or MRI [MRI preferred]) Other considered studies – RPR, UDS, EtOH level, EEG, CXR, EKG, HIV Detailed MED review – “medications, medications, medications” – medication must always be considered as potential contributors to the clinical presentation of “memory loss”

Evaluation of Memory Loss Patient with Known or Suspected Memory Loss CAM Abnormal Normal Identify Underlying Cause of Delirium & Treat No Delirium Equivocal or Inconsistent with Depression Consistent with Depression GDS Treat Depression or Discuss Options SWEET 16/ MMSE Impaired Not Impaired Re-evaluate After Treatment Lab Brain Imaging No Action

Vascular Dementia Onset of cognitive deficits with a stroke Abrupt onset of symptoms with stepwise deterioration Often neurological exam findings consistent with a prior stroke Infarcts on cerebral imaging Initially (i.e. the end of the 19th century) it was believed that dementia was the result of a chronic ischemia (i.e. a vascular pathology) but then in 1970, it was noted that amyloid + NFTs were more common than previously thought… so vascular pathology was thought to be more rare. Now with MRI/CT imaging, there is a resurgence of interest in the vascular pathology of dementia. Presently there are no validated criteria for diagnosing vascular dementia. A number of studies have demonstrated a high incidence of dementia after stroke with rates ranging from 6 to 32 percent in patients followed from three months to 20 years. “Clinical experience added to anecdotal evidence from the literature suggests that poststroke memory function may be reversible…. Five studies reported the prevalence of poststroke memory dysfunction at different poststroke intervals…. The prevalence of poststroke memory dysfunction varied from 23% to 55% 3 months poststroke, which declined from 11% to 31% 1 year poststroke… Not all patients with poststroke memory dysfunction 3 months after a stroke had memory dysfunction 1 year poststroke... Consequently, not all criteria for the dementia diagnosis were fulfilled any more… This may indicate that poststroke dementia may be reversible in a substantial proportion of patients with stroke… Preferably, standardized reassessment of cognitive function should be performed in each patient diagnosed with poststroke dementia1.” Age is a risk factor for the development of dementia after stroke. Clinically silent brain infarction is also a risk factor for subsequent cognitive decline. In one study, nondemented patients without a stroke history but with evidence of cerebral infarction on magnetic resonance imaging (MRI) had double the risk of dementia over five years of follow-up compared with controls with normal MRIs2. Although intracerebral hemorrhage is a possible contributor to vascular dementia, it is not generally described as such – perhaps because these are less likely to be recurrent events. Subarachnoid hemorrhage, cognitive impairment after cardiac bypass surgery, hypoxic ischemic encephalopathy, and watershed infarction in the setting of profound hypotension are vascular events that may cause permanent, devastating cognitive impairment. Features that suggest the diagnosis include: A stroke temporally correlates with the commencement of cognitive deficits Sudden start of symptoms followed by stepwise decline in global cognitive impairment A focused neurologic examination correlates with findings consistent with previous strokes Imaging that shows cerebral infarcts There is ongoing research that suggests a strong overlap between Alzheimer’s disease and vascular dementia – specifically there are experts who report not only shared risk factors but also shared pathogenesis. References: Snaphaan L, et al. Poststroke memory function in nondemented patients: A systematic review on frequency and neuroimaging correlates. Stroke. 2007;38(1):198-203. Vermeer SE, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348(13):1215-22.

Vascular Dementia Clinical Feature Value Abrupt Onset 2 Stepwise Detioration 1 Fluctuating Course Nocturnal Confusion Preservation of Personality Depression Somatic Complaints Emotional Incontinence HTN Hx Stroke Associated Atherosclerosis Focal Neurological Symptoms Focal Neurological Signs Hachinski Ischemic Index highlights clinical features Scores > 7 suggest vascular dementia Also of note: patients with vascular dementia are more likely to have impaired executive function than those with AD MRI Cerebral white matter lesions (WML) or leukoaraiosis on brain MRI is a nonspecific radiologic finding. These changes are somewhat ubiquitous in the normal as well as the demented elderly population. Radiographic criteria alone is insufficient to differentiate post-stroke dementia versus post-stroke without dementia. The presence of WML is significantly associated with age and hypertension. The burden of WML increases over time; age and hypertension are risk factors for disease progression. Lower vitamin B12 levels, and C reactive protein levels are also associated with WML. Data from pathologically verified cases show that an Hachinski Ischemic Index ≥7 has a sensitivity and specificity of about 90 percent for vascular dementia and good inter-rater reliability1. Reference: 1. Moroney JT, et al. Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias. Neurology. 1997;49(4):1096-105.

Vascular Dementia HTN DM Statins Aspirin Treatment Studies are beginning to suggest that patients with vascular dementia may benefit from the same drugs used to treat Alzheimer’s disease. This may be due to the fact that there is often overlap in these two commonly occurring illnesses or that the drugs have additional mechanisms of action or that there is a final common pathway in dementia. The exact reason for effectiveness is unclear but it should be further noted that there are no FDA-approved medications for the treatment of vascular dementia. There is some evidence that blood pressure lowering reduces the risk of incident dementia and slows cognitive decline. Mixed results have come from small trials looking at diabetes and vascular dementia. Statins have not yet shown themselves as proven therapies in this population. Anti-platelet therapy is well-established in secondary stroke prevention; there are no studies that assess prevention/treatment in vascular dementia.

Frontotemporal Lobe Dementia (FTD) Atrophy of the frontal and temporal lobes Absence of AD pathology Clinically: personality, behavior & language problems Impaired executive function In frontotemporal lobe dementia, cerebral atrophy (particularly in the frontal and anterior temporal lobes) is more pronounced than that seen in Alzheimer's disease (AD). Pathologists have coined the phrase "knife-edge gyri” to describe the pathological hallmarks. At times the predominance of cerebral atrophy in the frontal and temporal lobes can be seen on MRI and when present, will help differentiate FTD from Alzheimer’s disease. CNS Degenerative diseases are characteristically target specific neural structures – for example, in early AD, anterograde amnesia is the chief cognitive dysfunction; however in cases of frontotemporal lobe dementia the processes executive function are quite impaired early in during the course of the disease. The degeneration often occurs asymmetrically.

FTD Ages 35-70 years Rare after age 75 Familial occurrence in ~40% of cases More rapidly progressive disorder than AD Fatal Illness FTD is often diagnosed between the ages of 35 and 70 years, and much more rarely after age 75; the mean age of onset is the sixth decade. Notably the age of onset for FTD is often younger than that for Alzheimer's disease and is helpful to serve as a contrast between the two dementias (in Alzheimer’s disease the incidence increases significantly after age 75). “For individuals in their 60’s with dementia the prevalence of FTD is approximately the same as Alzheimer’s disease1.” Unfortunately, many FTD patients are mislabeled with Alzheimer’s disease with treatment with anti-cholinesterase inhibitors (which has not efficacy in FTD). Among dementia, the incidence FTD represents about 2-5%. FTD is equally prevalent in both genders. “Familial occurrence occurs in 40 percent of cases (about 40% of patients with FTD have family histories of a similar dementia syndrome) many of these individuals have a mutation of the tau protein gene on chromosome 17. Other mutations also occur. The remaining 60% of cases are sporadic1.” In FTD cognitive dysfunction and functional impairment progresses more rapidly than in AD – median survival has been estimated between 8.7 to 11.8 years. The pathogenesis is poorly understood, but we will cover what we do know in the next slide. Example: Consider a case of FTD in which degeneration (usually asymmetric) predominates in the dominant temporal lobe – the patient in this case initially presents with progressive aphasia without dementia. Reference: 1. Weiss BD. Elder Care: A Resource for Interprofessional providers. http://aging.medicine.arizona.edu Accessed: October 5, 2011.

FTD Pick’s disease is a subtype of FTD but was the first described Presence of Pick bodies (silver staining intracytoplasmic inclusion bodies) The diagnosis of Pick’s disease is based solely on the presence/absence of Pick bodies (approximately 10% of FTD is Pick’s disease). Figure (cerebral cortex hematoxylin and eosin stain): Note the inclusions called “Pick bodies” (arrowheads) which occur in neurons of the cerebral cortex. Although the pathogenesis of FTD is poorly understood, studies have shown a deficit of post-synaptic serotonin and has been attributed to some of the behavior dysfunction noted in the disease; it should further be noted that deficits in dopamine activity has also been observed in subsets of patients. Unlike Alzheimer’s disease – in FTD cerebral activity of acetylcholinesterase appears to be unaffected. Some studies indicate that the left hemisphere is primarily responsible for social extroversion and contact with others; the right hemisphere is more associated with social withdrawal and basic survival reactions. A healthy brain is balanced by showing both withdrawal and social interaction behaviors that are reality-based. Therefore, when frontotemporal diseases begin attacking the brain in only one hemisphere, behaviors may be very different depending upon the location of lesions. In general, damage to the right hemisphere results in the skills held by the left hemisphere becoming predominant (disinhibition and inappropriate hyper-sociality. The opposite happens when the left hemisphere is attacked first, leaving the right hemisphere predominant (apathy/abulia, poor motivation, negative demeanor). Bilateral degeneration results in several symptoms that together are often described by the family as “a personality change” in the patient. Note: All FTD is associated with a serotonergic deficit and decreased dopaminergic activity has been described; acetylcholinesterase activity is relatively intact

FTD Clinical Manifestations Inappropriate social behavior (conduct) <10% have short term memory impairment on testing @ initial presentation Poor insight into their condition Often mistaken for a psychiatric condition Behavior and personality change is the most useful feature for distinguishing FTD from other dementias (nearly 90% will be affected with this symptom during the course of their illness). Affected patients exhibit changes in social and personal conduct that are typically inappropriate to the situation; uninhibited and inappropriate social behaviors (stealing, use of foul language in public, inappropriate sexual behaviors). This has also been termed “dis-inhibited” behavior. This can be associated with a poor safety awareness (i.e. attempts to exit moving automobiles). There is a loss of awareness about behaviors. Most patients deny that they have a problem and have little insight into their condition. One study found that all patients with FTD, but especially those with prominent early behavioral changes, had much more profound deficits in self-awareness, self-monitoring, and self-knowledge compared with patients with AD. FTD patients are often mislabeled with psychiatric conditions because of their display of inappropriate social behavior early in the natural history of the disease. In contrast, appropriate behavior and social interaction is usually preserved early in the course of AD. Some have exhibited poor financial decision making and even demonstrated compulsive buying and has lead many an FTD patient to a diagnosis of bipolar disorder (and even schizophrenia). Initially, cognitive testing may be normal or only minimally abnormal. Only a small number (<10 percent) will have memory impairment on testing, despite the fact that many others complain of memory difficulty. There is often an increase in appetite that leads to continuous weight gain/eating. There can be other compulsive or repetitive behaviors (pacing, collecting things, and/or handwashing). Early progressive language dysfunction is the other main clinical presentation of FTD and has been called primary progressive aphasia. Photo: Microsoft Office Images #MP900448297 by Fotolia (http://office.microsoft.com/en-us/images/)

FTD: A Case A 68 year old male presents to subacute rehabilitation following a fall and subdural hematoma. A diagnosis of FTD was made two years prior to the incident via neuropsychological testing. Despite much improved mobility and function back to baseline, he was “made” long term care at a local nursing home, due to poor safety awareness (primarily concerns about wandering). Admission MMSE 21/30 (deficits noted below)/abnormal CDT 2/4 1/3 short term recall 1/5 serial sevens 0/1 pentagon 8/10 orientation FTD pre-dated fall head injury (subdural hematoma non surgery required) but was the reason for admission to ECF (Extended Care Facility) – family/expert opinion had been that he can’t be left alone because of concern about safety/wandering. He reports, “Look I need to get out of here; my wife is setting me up; she is taking my money and she’s trying to divorce me.” – in this case, a visit from his spouse or at a minimum a telephone call was the only thing that could calm him down. And then he ate my sandwich – he came into the office where I [the physician] had been working and he ate my sandwich – I caught him in the middle of the act (remaining sandwich in hand) and he said with his mouth full of food, “I didn’t eat your sandwich.” Our relationship had changed after that event – for at least 6 months to a year if we crossed paths in the hallway he would say, “and I didn’t eat your sandwich.” This would unusual for an Alzheimer’s patient to recall this event weeks and months later but FTD memory is often preserved in some areas. Later during the course of the disease he displayed the following – collecting towels, very poor self-hygiene – later he was noted with limited speech. Note to students: When FTD patients are tested on an MMSE there is initially noted impairment of PENTAGON/SERIAL SEVENS – there is an impairment of clock drawing as well.

FTD: A Case “I want to see what I can do about getting out of here?” He would go to report that his wife is taking his money and “she’s trying to divorce me you know.” Very often a visit from his wife (or a telephone call) was the only thing that could calm him down. Other behaviors were collecting towels, poor hygiene. Then… he ate my sandwich. FTD pre-dated fall head injury (subdural hematoma non surgery required) but was the reason for admission to ECF (Extended Care Facility) – family/expert opinion had been that he can’t be left alone because of concern about safety/wandering. He reports, “Look I need to get out of here; my wife is setting me up; she is taking my money and she’s trying to divorce me.” – in this case, a visit from his spouse or at a minimum a telephone call was the only thing that could calm him down. And then he ate my sandwich – he came into the office where I [the physician] had been working and he ate my sandwich – I caught him in the middle of the act (remaining sandwich in hand) and he said with his mouth full of food, “I didn’t eat your sandwich.” Our relationship had changed after that event – for at least 6 months to a year if we crossed paths in the hallway he would say, “and I didn’t eat your sandwich.” This would unusual for an Alzheimer’s patient to recall this event weeks and months later but FTD memory is often preserved in some areas. Later during the course of the disease he displayed the following – collecting towels, very poor self-hygiene – later he was noted with limited speech. Note to students: When FTD patients are tested on an MMSE there is initially noted impairment of PENTAGON/SERIAL SEVENS – there is an impairment of clock drawing as well.

FTD The FDA has not approved any drugs to treat this condition. Memantine is presently being studied. FTD: often respond adversely to cholinesterase inhibitors with increased agitation and insomnia – again see pathology notes (“preserved acetylcholinesterase system”).

FTD vs AD Characteristic FTD Alzheimer’s Disease Age of Onset <70 and even < 65 Usually greater >65 Memory Deficits Late Early Executive Function Deficits Behavioral Disturbance Brain Imaging Frontotemporal Atrophy Diffuse Atrophy Response to Cholinesterase Inhibitors None Some Family Hx ~ 40% With Alzheimer’s disease, typically age of onset is greater than 65 – exceptions to this rule are when Alzheimer’s disease is of a familial origin. This is in contrast to FTD (for example, it would be unusual to diagnose FTD in an 80+ individual). Cholinesterase inhibitors, widely used for Alzheimer’s disease, have no benefit in FTD and have caused worsening symptoms in some patients. The role of memantine (Namenda®) is being studied. Reference: Weiss BD. Elder Care: A Resource for Interprofessional providers. http://aging.medicine.arizona.edu Accessed: October 5, 2011. Weiss BD. Elder Care: A Resource for Interprofessional providers. http://aging.medicine.arizona.edu Accessed: October 5, 2011.

Lewy Body Dementia DLB is the 3rd most common dementia after AD Progressive gradual dementia Fluctuations in cognitive function Persistent, well-formed hallucinations Spontaneous motor features of parkinsonism Pathogenesis Lewy bodies are round, eosinophilic, intracytoplasmic inclusions in the nuclei of neurons. In Lewy body dementia, Lewy bodies are often found in the anterior frontal and temporal lobes, the cingulate gyrus, and the insula. They can also be found in the substantia nigra and locus ceruleus (and other brainstem nuclei) which makes the pathology of Lewy body dementia very similar to Parkinson’s disease. NFTs, the hallmark of Alzheimer’s disease, are sparse in Lewy body dementia. Amyloid plaques are seen in most cases of DLB but may be less numerous than in AD2. At autopsy, most patients with DLB meet plaque burden criteria for AD (again there does appear to be an overlap in the pathogenesis of the disease). Diagnosis (2/3 core features) The biggest barrier to the diagnosis of Lewy body dementia is a low index of suspicion. The cardinal features of DLB which suggest the diagnosis may not be volunteered by patients or caregivers and often require specific solicitation by the clinician – a patient must have dementia and 2 out of 3 of the core clinical features: Fluctuations in cognitive function, hallucinations, Parkinsonism In diffuse Lewy body dementia, ATTENTION (i.e. “Fluctuations in Cognitive Dysfunction”, EXECUTIVE FUNCTION and VISO-SPATIAL DISTURBANCES occur early in the disease and are more of a problem than memory disturbances. Fluctuations in cognitive function -- The severity, duration, and type of symptoms involved in fluctuations is quite varied, for a given patient. Episodes can be subtle, as in a brief decline in ability to perform an activity of daily living, or they may be dramatic enough to raise the question of a stroke or seizure (i.e. mistaken for delirium). Hallucinations: Visual hallucinations occur in approximately two-thirds of patients with DLB, and are relatively rare in AD. These are frequently an early sign in DLB. Hallucinations occur often in a setting of person having no prior psychiatric history (i.e. schizophrenia). Parkinsonism — Parkinsonian symptoms, brady- and akinesia, limb rigidity, and/or gait disorder, are seen in approximately 70 to 90 percent of patients with DLB, and they can be as severe as in idiopathic Parkinson's disease (PD). However, parkinsonian features are usually more bilaterally symmetric and milder than in PD MRI Generalized atrophy and white matter lesions are nonspecific findings in dementia. Recall that MRI coronal sections through the hippocampus usually show a greater degree of hippocampal atrophy in Alzheimer disease compared with Lewy body dementia. References: 1. Harrington CR, et al. Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein. Dementia. 1994;5(5):215-28. 2. Barber R, et al. Dementia with Lewy bodies: diagnosis and management. Int J Geriatr Psychiatry. 2001;16 Suppl 1:S12-8.

Lewy Body Dementia: A Case An 81 year old former PhD psychologist is transferred to assisted living from her independent living home due to significant increased deficits in her functional status – including multiple falls, inability to self-administer medications, a reversal of the sleep-wake cycle, and profound weight loss Admission MMSE: 28/30 (+) deficit 3/5 serial sevens Admission Weight: 108 lbs During the next four weeks there is stabilization of the sleep-wake cycle and weight gain (112 lbs) Former psychologist but clearly exhibiting signs of dementia – for example, she was observed to need verbal cuing and some physical assistance with ADLs but continued to score well on the MMSE – this was attributed to IQ + prior experience with cognitive testing. Never-the-less she did eventually need assistance with dressing . A walker was added after recurrent falls noted despite continued PT/OT efforts. Some days clearly better than others. It was noted that she “Saw a mouse run across her ceiling x two” – this was investigated and unfounded. Eventually she was transferred from “regular” assisted living to an specialized dementia unit assisted living. 6 months after transfer to the specialized unit she was noted to have (+) cogwheel.

Lewy Body Dementia: A Case During the next year, despite several falls that responded to physical therapy she continues to need considerable more help dressing as well as orientation/cuing (i.e. meals and medication times). Observation from nursing is that she is just “lost” and even ostracized by other residents. On two separate occasions she reported that she saw a mouse running across the ceiling. It was investigated in earnest but no evidence of mice could be found. Former psychologist but clearly exhibiting signs of dementia – for example, she was observed to need verbal cuing and some physical assistance with ADLs but continued to score well on the MMSE – this was attributed to IQ + prior experience with cognitive testing. Never-the-less she did eventually need assistance with dressing. A walker was added after recurrent falls noted despite continued PT/OT efforts. Some days clearly better than others. It was noted that she “Saw a mouse run across her ceiling x two” – this was investigated and unfounded. Eventually she was transferred from “regular” assisted living to an specialized dementia unit assisted living. 6 months after transfer to the specialized unit she was noted to have (+) cogwheel.

Lewy Body Dementia: A Case She is transferred to a specialized dementia unit in which her behavior (now observed more closely) is vastly different than other’s with Alzheimer’s dementia. One year later (+) cogwheel rigidity is noted. Former psychologist but clearly exhibiting signs of dementia – for example, she was observed to need verbal cuing and some physical assistance with ADLs but continued to score well on the MMSE – this was attributed to IQ + prior experience with cognitive testing. Never-the-less she did eventually need assistance with dressing . A walker was added after recurrent falls noted despite continued PT/OT efforts. Some days clearly better than others. It was noted that she “Saw a mouse run across her ceiling x two” – this was investigated and unfounded. Eventually she was transferred from “regular” assisted living to an specialized dementia unit assisted living. 6 months after transfer to the specialized unit she was noted to have (+) cogwheel.

Lewy Body Dementia The FDA has not approved any drugs to treat this condition. Unresponsiveness to Parkinson’s medication Supportive clinical features of DLB include sensitivity to neuro-leptic medications (i.e. anti-psychotics) as well as anti-dopaminergic medications (i.e. Metoclopramide)

Lewy Body Dementia vs. AD Characteristic Lewy Body Dementia Alzheimer’s Disease Age of Onset >65 Usually >65 Memory Deficits Late Early Executive Function Deficits Visual Disturbance 2/3’s of Patients Rare (or very late) Brain Imaging Diffuse Atrophy Response to Cholinesterase Inhibitors Not FDA approved Family Hx Sporadic The Mini-Mental State Examination (MMSE) can be helpful to differentiate among dementia types (especially during early phase). The early appearance of impaired figure copying (overlapping pentagons), clock drawing, and serial sevens (or spelling WORLD backward) is suggestive dysfunction in executive function which implies DLB (or FTD). This can be an important clue – a patient with impaired executive dysfunction but preserved recall. It has been estimated that 0.7% of individuals older than age 65 have Lewy body dementia1. The mean age at presentation is approximately 75 years old. Most cases are sporadic although familial type cases have been described in the literature. Reference: 1. McKeith I, et al. Dementia with Lewy bodies. Lancet Neurol. 2004;3(1):19-28.

Parkinson’s Disease Dementia Estimated six-fold increased risk for becoming demented compared with people without the disorder. Dementia typically occurs in the last half of the PD clinical course (whereas, in DLB, it’s the presenting feature) Executive dysfunction is a hallmark feature Parkinson’s disease can clearly co-exist with other dementias (i.e. Alzheimer’s disease) but there is increasing evidence to support dementia as a clinical feature of the disease itself (never-the-less, this remains a controversy). Some have speculated that Parkinson’s disease dementia and Lewy body dementia are the same disease but with different presentations. A comparison of neuropsychologic test profiles of patients with Lewy body dementia and Parkinson’s disease dementia found no significant differences. Dementia (when it occurs) in Parkinson’s disease evolves during the mid-stage or end the natural history of Parkinson’s disease; this is in contrast to Lewy body dementia in which cognitive dysfunction the presenting feature. Simply put – dementia does not occur early in Parkinson’s disease. Recall core motor features of Parkinson's disease include: Brady- and akinesia Rigidity Resting tremor Postural instability Again – executive function is impaired early during the dementia from Parkinson’s disease (while recall is often preserved).

Parkinson’s Disease Dementia Rivastigmine (Exelon®) has been approved for use in mild-to-moderate Parkinson’s related dementia. Treatment Rivastigmine (Exelon®) has been approved for use in mild-to-moderate Parkinson’s related dementia.

Normal Pressure Hydrocephalus (NPH) “Classic Triad” of symptoms: Dementia Gait Disturbance Urinary Incontinence Pathologically enlarged ventricular size Normal opening pressures on lumbar puncture Potentially reversible by the placement of a ventriculoperitoneal shunt

HIV Associated Dementia Age is a significant risk factor in HIV-associated dementia Clinical Symptoms Distractibility/Poor Concentration Mood Changes/Apathy vs Lability Gait Dysfunction/Clumsiness Reduced psychomotor speed Absence aphasia, agnosia, & apraxia (until late disease course) helps distinguish from AD More than a quarter of Americans living with HIV/AIDS are aged 50 or older, and 17% of newly diagnosed cases occur in this age group. One longitudinal study compared 106 HIV-infected patients >50 years of age to 96 patients ranging from 20 to 39 years of age. After controlling for education, race, substance abuse, antiretroviral medication use, viral load, CD4 T-cell count, and Beck Depression Inventory score – age was associated with increased risk of dementia. HIV associated dementia is noted for the following symptoms- impaired memory, psychomotor speed impairment, depressive symptoms and movement disorders. Patients with HIV-1 often become demented early in the disease. They show quite striking mood changes (either severe lability or severe apathy). Fine motor skills deteriorate quickly and they are hyper-reflexive. They are prone to accidents such as tripping, falling and stumbling because of coordination problems. They often require nursing home care, even at young ages, because of missing family support systems.

Huntington’s Disease (HD) Huntington’s Disease - traced to emigrants (1630) from East Anglican village of Bures, England: - Dominant inheritance (1 parent with gene) - CAG - Choreoathetosis starting at 35-45 years of age - Dementia & emotional lability also Huntington’s disease (HD) symptoms were first documented in 1630 in England, but cases probably occurred before that time. This disease can be diagnosed using genetic testing; 40 or more CAG-repeats results in a neuro-toxic condition that destroys brain cells, causing a triad of deficits: 1) movement disorders (primarily chorea although there are cases without this symptom); 2) emotional lability; 3) cognitive and judgment decline. Any of these symptoms can appear initially, and they usually start in mid-life (30’s and 40’s). However, the number of CAG repeats is associated with the age at which problems begin (i.e., 67 repeats was reported in a patient who was symptomatic at age 20 years). This disease is autosomal dominant, meaning that only one parent is needed to pass on the disease. Research is attempting to find medicinal treatments that will reduce or eliminate the toxic effects of CAG-repeats so degenerative symptoms never appear.

Creutzfeldt-Jakob Disease Rapidly progressive dementia Pathogenesis: Prions Typically fatal within 1-2 years after symptom onset Motor deficits & seizures often occur Not treatable Potentially transmissible No clear cut MRI findings Rapid progression (i.e. 2 years from onset to death) There are no hallmark findings on MRI to identify CJD; however, functional imaging show diffuse metabolic abnormalities Once the disease is transmitted, the malignant conformation of proteins can induce proteins in the native form to convert to the malignant form – this triggers a cascade of events.

Alcoholic Dementia Alcoholic dementia Cerebellar and corpus callosum atrophy Affective prosody comprehension decline Gait problems Abstract reasoning decline more than education knowledge Unpredictable and varied in presentation as well as progression Alcoholic dementia is revealed by symptoms of gait instability due to cerebellar atrophy, both emotional lability and abstract reasoning decline, and very poor ability to detect emotion in the voices and faces of others.