Part 1: Introduction, Head and Neck, and Cranial Nerves

David J. Gladstone, BSc, MD, Fellow, Cognitive Neurology and Stroke Research Unit, Sunnybrook and Women's College Health Sciences Centre and Division of Neurology, University of Toronto, Toronto, ON.

Sandra E. Black, MD, FRCPC, Professor of Medicine (Neurology), University of Toronto; Head, Division of Neurology and Director, Cognitive Neurology Unit, Sunnybrook and Women's College Health Sciences Centre, Toronto, ON.

Abstract
This four-part series of articles provides an overview of the neurological examination of the elderly patient, particularly as it applies to patients with cognitive impairment, dementia or cerebrovascular disease. The focus is on the method and interpretation of the bedside physical examination; the mental state and cognitive examinations are not covered in this review. Part 1 begins with an approach to the neurological examination in normal aging and in disease, and reviews components of the general physical, head and neck, neurovascular and cranial nerve examinations relevant to aging and dementia. Part 2 covers the motor examination with an emphasis on upper motor neuron signs and movement disorders. Part 3 reviews the assessment of coordination, balance and gait. Part 4 discusses the muscle stretch reflexes, pathological and primitive reflexes, sensory examination and concluding remarks.

Chris MacKnight, MD, MSc, FRCPC, Assistant Professor, Division of Geriatric Medicine, Dalhousie University, Halifax, NS.

Introduction
Lewy body disease is one of the many conditions causing dementia. As it is relatively common, and has an effective management distinct from that of Alzheimer disease,¹ all physicians who see older adults should have some familiarity with Lewy body disease.

Diagnosis
Lewy body disease is underdiagnosed.² It should be suspected in an older adult who presents with cognitive impairment (even if quite mild) in addition to hallucinations or parkinsonism. Clinical criteria are presented in Table 1.^3,4 The criteria of fluctuation have proven difficult to apply at the bedside, but clinical tools are now available.⁵ The parkinsonism is often mild and subtle, and is more often rigidity than tremor. An important feature is neuroleptic sensitivity. Up to 80% of these patients can, even with low doses, develop reactions to neuroleptics or atypical agents, which are often severe.⁶ Extrapyramidal symptoms and cognitive decline are the most common manifestations. The decline can be permanent, and neuroleptic malignant syndrome can occur. This likelihood of reaction to neuroleptics is one of the chief reasons to be familiar with the disorder and to have a low threshold to at least suspect its presence.

It can sometimes be difficult to distinguish Lewy body disease from Alzheimer disease, Parkinson's disease or delirium.

Deborah Hebert BSc(0T), MSc(Kin) PhD candidate, Ontario Institute for Studies in Education, Clinical Educator (OT), Toronto Rehabilitation Institute Clinical Associate, Department of Occupational Therapy, University of Toronto.

Eric Roy PhD, C Psy, Professor, Departments of Kinesiology and Psychology, University of Waterloo, Graduate Department of Rehabilitation Science University of Toronto, Toronto, ON.

When a person with neurological impairment engages in an unusual action such as pouring hot water into a cup with no tea bag and stirring it with a fork, or cutting bread with a knife oriented upside down and sideways, the impairment of limb apraxia should be suspected. Apraxia has been defined as, " a neurological disorder of learned purposive movement skill that is not explained by deficits of elemental motor or sensory systems".¹ While motor problems such as abnormal tone and posture, paresis, ataxia and dysmetria can coexist with limb apraxia,^2,3 this movement problem is one of conceptual understanding of action and/or production of movement.⁴ The deficit cannot be explained by intellectual deterioration, lack of cooperation, sensory disturbances, agnosia, disrupted body schema, visuospatial disturbances or aphasia.^3,5 There is evidence that aphasia and apraxia commonly co-occur, as they are predominantly found in right-handed clients with left hemisphere lesions; however, they are often clearly dissociated.

Taresa Stefurak MSc, MD, FRCPC, Neuropsychiatry Fellow, Rotman Research Institute, Baycrest Centre for Geriatric Care, University Health Network, Department of Neurology, University of Toronto, Toronto, ON.

Introduction
Although Parkinson's disease (PD) is by definition a movement disorder, with a clinical diagnosis made by the presence of two out of three cardinal levodopa-responsive motor signs (tremor, rigidity, bradykinesia), both cognitive and neuropsychiatric symptoms are also important components. The clinical impact of these neurobehavioural symptoms is supported by a study in which the strongest predictor of quality of life perceived by PD patients was the presence of depression.¹ Cognitive impairment as well as postural instability and disability also contributed to poor quality of life. Behavioural disturbances and dementia are the primary reasons for nursing home placement in PD patients.²

Characterizing the nature of these symptoms in PD provides an important model to understand the underlying mechanisms of disease progression and brain function. Although psychosocial aspects may play a role in some of the behavioural and mood disturbances in PD, evidence suggests that the underlying mechanism for these symptoms arises from the biological dysfunction of anatomical and neurochemical substrates that occur in PD.

Céline Chayer MD, FRCPC, Behavioural Neurology, Hôpital Maisonneuve Rosemont, Montreal, PQ.

Introduction
The prevalence of dementia in Canada has been estimated at 8%, after the age of 65 years.¹ Alzheimer disease (AD) accounts for approximately 60% of cases, while other conditions accounting for the remaining 40% include, among others, vascular dementia, dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). Differences in prognosis and symptomatic treatment, as well as eventually disease-modifying therapy underline the importance of the differential diagnosis of dementia. The use of clinical criteria for diagnosis of degenerative and vascular dementias can increase the level of clinical diagnosis accuracy² and should, therefore, be known by physicians dealing with dementia. Advances in the understanding of FTLD have been made over the past 15 years. We will review the clinical manifestations of FTLD and highlight the differences with AD.

Pick's disease, fronto-temporal lobar degeneration and Pick complex
In 1892, Arnold Pick described patients with predominant language impairment in whom focal atrophy of the frontal and temporal lobes was found.³ Later, Alois Alzheimer described, in Pick's original patients, ballooned cortical neurons containing cytoplasmic inclusions that were subsequently called Pick bodies. Pick's disease became synonymous with frontotemporal dementia.

Karl Farcnik, BSc, MD, FRCPC, Psychiatrist, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.
Michelle Persyko, Psy.D, C.Psych, University of Toronto, Toronto, ON.
C. Bassel, M.A., University of Toronto, Toronto, ON.

Introduction
Aphasia has been described as a disorder of verbal communication due to an acquired lesion (or lesions) of the central nervous system involving speech production and/or comprehension.¹ Aphasia does not involve deficits in global processes of communication, but only in its linguistic component, as evidenced by patients' ability to communicate through other means (e.g., complex nonverbal gestures).² Aphasia is an integral part of the clinical presentation in Alzheimer Disease (AD). It is also an important diagnostic feature of other neurological disorders, which may be distinctive or overlap with AD. Clinicians should have a conceptual understanding of the different forms of aphasia as well as the conditions with which they are associated. The authors will review the diagnosis, assessment and treatment of aphasia, in the context of AD, Primary Progressive Aphasia (PPA), Frontotemporal dementia (FTD) and stroke.

The major types of aphasia can be classified as either fluent or nonfluent.

Ailsa KR Cook, BSc
Research Fellow, Centre for Social Research on Dementia,
Department of Applied Social Science, University of Stirling, Stirling, UK.

 

Pain Assessment in Patients with Dementia
Pain is an important consideration when caring for patients with dementia. Being in pain leads to cognitive (e.g. poor concentration) and behavioural (e.g. apathy) symptoms, which if left untreated, exacerbate the effects of the existing cognitive impairment.^1,2 Pain is also associated with increased depression amongst people with dementia, as well as increases in other behavioural disorders, such as calling out and aggression.^3,4,5,6

Despite its significant negative impact, research has shown that many older people with dementia experience untreated pain.^7,8,9,10 A survey of 13,625 older cancer patients living in nursing homes revealed that 26% of those with daily pain received no analgesics, and a disproportionate number of this group were cognitively impaired.⁷ Similarly, a review of analgesic use in nursing homes found that residents with dementia were prescribed and administered fewer analgesics than were their cognitively intact counterparts.⁸

If pain management in this population is to improve, it is essential that health care professionals pay more attention to the assessment of pain in patients with dementia.

Wendy S. Meschino, MD, CCFP, FRCPC, FCCMG
Clinical Geneticist,
North York General Hospital,
Toronto, ON.

 

"My mother has Alzheimer disease. Can I be tested to see if I carry the gene?" Such questions from patients are likely to be a familiar refrain to many physicians. While there is a great deal of discussion regarding the potential hereditary aspects of Alzheimer disease (AD), genetic testing is not appropriate for the vast majority of patients or their unaffected relatives. Genetic testing is possible only in selected situations where there is a significant family history of early-onset disease. In this article, we will explore how to take a family history of Alzheimer disease, how to recognize when genetic testing is appropriate, the critical issues to be discussed in genetic counselling and a brief review of the genes identified to date which are associated with familial Alzheimer disease (FAD).

In taking a family history, it is important to inquire about affected and unaffected relatives on both sides of the family. Details of the family history may be recorded in pictorial form as a pedigree (Figure 1). A minimum of three generations should be noted including siblings, parents, aunts, uncles, cousins and grandparents.

Christine Oyugi, BSc
Managing Editor,
Geriatrics & Aging.

Edited by:
Karl Farcnik, BSc, MD, FRCPC
Psychiatrist, Division of
Geriatric Psychiatry,
University Toronto,
Part-time staff,
Toronto Western Hospital, Toronto, ON.

Contributions from:
Morris Freedman, MD, FRCPC
Director, Behavioural Neurology
Program, Baycrest Centre for Geriatric Care and Staff Scientist,
Rotman Research Institute, Toronto, ON.

Helena C. Chui, MD
Professor of Neurology,
University of Southern California
Los Angeles, Ranchos Los Amigos
National Rehabilitation Center, Downey, CA, USA.

Ian McKeith, MD, FRCPsych
Professor of Old Age Psychiatry,
Institute for Health of the Elderly
University of Newcastle Upon Tyne, UK.

• What are the clinical features of Frontotemporal and Lewy Body Dementias?
• What is the relationship between dementia and vascular disease?
• How would you differentiate among the different dementias?
• Does determining the distinction between Mild Cognitive Impairment and dementia have any clinical relevance or is it merely an academic exercise?

These are a few of the topics that were addressed by speakers during the last day of the 11th Annual Rotman Conference. This article summarizes the points presented during the last day of this conference on Tuesday, March 20th.

Dr. Morris Freedman, Director of the Behavioural Neurology Program at Baycrest Centre for Geriatric Care and a Staff Scientist at the Rotman Research Institute in Toronto, provided an extensive clinical review of frontotemporal dementia (FTD). The features of FTD are important for the differential diagnosis of this disease from Alzheimer disease (AD). Patients with FTD have marked personality and emotional changes that include loss of social awareness, and antisocial or disinhibited behaviour (e.g. use of rude speech, neglect of personal hygiene and grooming); they may also become easily distracted. These patients typically have poor insight and may not recognize that they have any behavioural problems. Other features include overeating, excessive smoking, oral exploration of objects and stereotypical behaviour such as wandering.

Language is a key factor in distinguishing FTD from AD. FTD patients have early preservation of language, in contrast to the situation in AD patients where language is primarily affected early in the course of the disease. As AD patients become more impaired, they develop fluent aphasia with comprehension problems. FTD patients experience a reduction in speech capacity, which may eventually lead to mutism, but their comprehension is relatively preserved. Memory loss in FTD is variable and not as severe as that with AD.

The pathophysiology of FTD involves the anterior temporal and frontal lobes. There are two forms of neuropathology--a microvacuolar form and a gliotic form. The microvacuolar form involves the general loss of neurons, microvacuolar degeneration (a spongiform-type of change), a mild astrocytic gliosis and primarily involves laminae I-III. There are no Pick cells or bodies that are seen in Pick's disease, but clinically one cannot differentiate between Pick's disease and FTD. The gliotic form of FTD represents the pathology of Pick's disease and involves all the cortical layers. There is intense astrocytic gliosis and Pick bodies may be present. There has been some debate as to whether the microvacuolar form and the Pick-type pathology represent the same or different disorders.

FTD has an earlier age of onset than does AD; the average age of onset is between 50-60 years of age. The disease duration averages 8-10 years. Although the precise cause of FTD remains unknown, there is a genetic predisposition to the disease in some patients. Fifty percent of patients with FTD have a positive family history and up to 18% have an abnormality on chromosome 17 (autosomal dominant).

There is also a relationship between FTD and motor neuron disease; some patients with FTD also develop motor neuron disease, symptoms of which can appear before or after the onset of FTD. If a diagnosis of FTD is made, it is important for physicians to be aware of the co-occurrence of motor neuron disease.

FTD patients have normal EEG results in the early phases of the disease--in fact an abnormal early EEG argues against a diagnosis of FTD. SPECT analysis shows deficits in frontal and temporal perfusion; however, this is not a diagnostic feature, as AD patients can have the same feature. Neuropsychological assessments show a marked deficit on frontal tests, with an absence of severe amnesia and perceptual 'parietal' deficits (e.g. copy to command is still good).

FTD is one of three prototypical clinical syndromes comprising the broader entity of frontotemporal lobar degeneration: Frontotemporal dementia (FTD), Primary Progressive Aphasia (PPA) and semantic dementia (SD). The difference among the three conditions is based on the location of the pathology--FTD is frontotemporal, SD involves lesions in the temporal lobes bilaterally, and PPA involves left frontotemporal pathology. SD, more so than either FTD or PPA, is easily confused with AD--similar to patients with AD, these patients have fluent speech and comprehension deficits. But unlike those with AD, these patients lose the meaning of words and objects with relatively good preservation of memory. PPA is less likely to be confused with AD because patients' speech becomes non-fluent.

Although patients show serotonergic deficits, there are currently no drugs available for the treatment of FTLD. SSRI's may improve some of the behavioural problems. As patients do not have cholinergic deficits, cholinesterase inhibitors will not help and may actually aggravate symptoms.

Dr. Ian McKeith, Professor of Psychiatry from the Institute of Health in the Elderly in Newcastle, England, updated the conference attendees on the current understanding of Lewy Body Dementia. Lewy body dementia (DLB) accounts for 15-20% of all dementias in old age, but has only been widely recognized since the mid-1990s. The clinical phenotype of Lewy Body Dementia (DLB) is related to the site, severity and amount of Lewy body pathology. DLB is characterized by the presence of Lewy bodies in the brainstem (substantia nigra and locus coeruleus), and in the subcortical (nucleus basalis of Meynert) and cortical regions of the brain. Neuronal loss and gliosis are also present in those areas. In some cases, there is an overlap between DLB, AD and Parkinson's disease (PD). As is the case in patients with both AD and PD, DLB patients have b-amyloid plaques and neurofibrillary tangles in their brains, although not in sufficient numbers to make a diagnosis of AD. The core clinical features of DLB include fluctuating cognitive impairment (seen in 80% of patients), persistent visual hallucinations (70% of patients) and Parkinsonism (75% of patients). These features are used to distinguish between DLB patients and AD patients (See Table 1). Other features which are supportive of DLB but lack specificity are: transient lack of consciousness (40%), falls and syncope (50%), systematized delusion (70%), neuroleptic sensitivity (50%), depression (50%) and REM sleep disorder (no estimates available). DLB is commonly mis-diagnosed as AD, as patients are equally impaired on both the MMSE and the Cambridge Cognitive Examination (CAMCOG). However, DLB patients perform worse on tests of attention (e.g. reaction time), visuospatial performance (e.g. clock drawing) and visual perception (e.g. fragmented letters). A Consensus guideline for the clinical and pathological diagnosis of dementia with Lewy bodies was developed in 1996. Several studies have been performed to validate these criteria and have found that the Consensus criteria for DLB performed as well in prospective studies as did those for AD and vascular dementia (VaD), with a high diagnostic sensitivity. Fluctuation is an important diagnostic indicator, reliable measures of which need to be further developed. Although specificity of the clinical diagnostic criteria is generally high, 17-78% of cases may be missed. This may be attributed to clinicians being unaware of the criteria or unfamiliar with the diagnosis. The potential contribution of neuroimaging to the differential diagnosis of DLB from other dementias remains uncertain, although relative preservation of the hippocampus and temporal lobe is found in DLB when compared with AD.

TABLE 1 Core Clinical Feature of DLB vs. AD
Clinical Feature	DLB	AD
Fluctuating Cognitive Impairment	80%	60%
Persistent Visual Hallucinations	70%	15%
Parkinsonism (bradykinesia, rigidity, gait)	75%	20%

Currently, there is no treatment that stops the progression of DLB. Much of the focus on treatment has been the management of the neuropsychiatric symptoms of the disease and the associated movement disorders. Unfortunately, 50% of patients show sensitivity to older neuroleptics including haloperidol and phenothiazines, and these patients are more likely to die than are those not treated with these drugs. However, newer antipsychotics such as olanzapine and quetiapine may be relatively safer for the management of DLB. Recent studies have shown a benefit of acetylcholinesterase inhibitors with respect to the treatment of behavioural, as well as cognitive, aspects of this disease, and it is possible that these drugs could become the treatment of choice in the future.

Dr. Helena Chui, a Professor from the University of Southern California, gave a talk on cognitive impairment due to subcortical ischemic vascular disease.

Ischemic vascular disease (IVD) is a common cause of dementia in the Western world. Similar to the situation with AD, the incidence of VaD increases with age. However, the exact incidence and prevalence of VaD is difficult to discern. The major problem remains the disagreements with regards to diagnostic criteria and their implementation. In particular, there is uncertainty regarding the following:

1. The classification of patients who show both vascular and degenerative features (mixed-dementia);
2. The difficulty choosing among several different clinical criteria (e.g., the Hachinski Ischemic Score);
3. The use of imaging findings in defining VaD;
4. The minimal level of disease severity required for a patient to be included in epidemiologic studies.

The problem in diagnosing vascular dementia lies in the causal relationship. It is not very difficult to diagnose dementia and, with the recent advancements in structural imaging, it is also not very difficult to diagnose vascular disease. The conundrum is--what is the relationship between the two and how do we know that the vascular lesion seen in imaging is causing the dementia syndrome? According to Dr. Chui, the term Vascular Dementia is too broad. VaD is not a disease, but only one possible phenotypic expression of vascular brain injury. For this reason, her talk focused on subcortical ischemic vascular dementia (SIVD). There are many types of cerebrovascular disease, leading to variable clinical and symptomatic expressions (Figure 2). There are a number of guidelines available on the effective treatment of risk factors that lead to these conditions and this should be the focus of SIVD management. The frequency of SIVD seems to vary depending on the ethnic group; it is more common in persons of Japanese or African American descent.

The small vessels affected in SIVD are within the brain parenchyma and are small penetrating arterioles approximately 100 to 600 mm in diameter. The predominant risk factors for SIVD are diabetes mellitus, hypertension, amyloid angiopathy (a subset of AD), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). SIVD is a term that can be used for either the disease or the dementia syndrome. According to Dr. Chui, SIVD represents a more homogeneous clinical and pathological entity, which may be a more useful target for treatment, especially if the target is the cerebrovascular disease and cerebrovascular brain injury rather than its symptomatic expression.

There are two proposed underlying pathophysiologic mechanisms of how SIVD leads to ischemic brain injury--Occlusion and Hypoperfusion. Occlusion leads to small lacunar complete infarcts, cystic necrosis, and loss of all tissue elements (neurons, axons, glia, astrocytes). It leads to a more homogeneous phenotype including subcortical dementia, affective disorder such as depression, extrapyramidal signs and pure motor and sensory deficits. Hypoperfusion results from widespread narrowing of small penetrating arterioles, leading to incomplete infarction where there is a selective loss of tissue elements. For instance, in the white matter there will first be a loss of oligodendrocytes with demyelination, astrogliosis and, later, a loss of axons. Hypoperfusive ischemic brain injury has been postulated to be the cause of Binswanger syndrome, which is characterized by a combination of deep white matter changes, as well as a slowly progressive subcortical dementia, gait disturbance and urinary incontinence.

Our current understanding of how cognitive impairment relates to SIVD hinges on the lacunar hypothesis. This hypothesis states that the likelihood of dementia is related to the number, size and location of lacunar infarcts within parallel frontal subcortical loops (Prefrontal Cortex-caudate-globus pallidus-thalamus-PFC). However, recent imaging studies showed that the best correlate between dementia and SIVD was atrophy and not the volume or the number of lacunar infarcts. Clinical evaluation of SIVD should include tests of working memory, recognition memory and executive function.

The treatment of SIVD can be divided into three components. The first is primary prevention, where one tries to prevent infarction or vascular cognitive impairment by managing vascular risk factors such as hypertension and diabetes. For secondary prevention, where there is evidence of vascular brain injury--infarction, incomplete infarction or vascular cognitive impairment--the goal is to prevent the recurrence or the progression of disease. There is evidence that, even at this stage, one should continue to manage hypertension but also administer other treatments. Tertiary treatment refers to symptomatic treatment of memory and cognitive impairment. Acetylcholinesterase inhibitors are currently being studied for this purpose; currently, none have been approved for this purpose.

Dr. Chertkow, Associate Professor of Neurology and Neuropsychiatry at McGill University, presented a talk on high and low technological approaches to the early diagnosis of AD. According to Dr. Chertkow, the goal in trying to delineate an early mild cognitively impaired group is to identify which individuals will or will not deteriorate over finite periods of time (5-10yrs). One of the difficulties in studying individuals with Mild Cognitive Impairment (MCI) is the lack of accepted diagnostic criteria. A diagnosis of MCI can be made if patients meet the following criteria: (a) complain of defective memory; (b) normal activities of daily living; (c) normal general cognitive function; (d) abnormal memory function for age; and (e) absence of dementia. However, there are varying inclusion criteria that may overlap with the aforementioned.

Some researchers contend that patients with MCI may be an in-between group (i.e. individuals who are between normal aging and mild AD) (See Dr. Petersen's talk). The issue is to prognosticate and to define those who are going to progress from this state and those who will not. Prognosis in MCI varies depending on how you characterize your group, but severity of symptoms often predicts progression to AD. Researchers are trying to identify biological and cognitive markers that will assist the general physician in delineating MCI individuals who will progress to AD in a finite time period. The characteristic of a good marker is that it should be precise and simple, should be inexpensive, should be reliable and non-invasive and should have the ability to be validated in pathological cases. Recently, Chertkow and colleagues completed a study on mild memory loss in the elderly. The study looked at 90 individuals who passed the above criteria for MCI and followed them for 3-5 years. Over the course of the study, 51 patients deteriorated to dementia (50 of them meeting the criteria for probable AD) and 39 did not deteriorate. Initially, about 15-17% of the MCI individuals progressed to AD each year; however, even after 10 years, approximately 15% of the individuals did not have dementia and did not appear to be progressive. Therefore, there is a subgroup of MCI patients who do not progress to AD.

There were some interesting differences between those individuals that progressed to AD and those that did not. The progressing group had an older age of onset of their symptoms and performed slightly worse on the MMSE at the time of presentation. The researchers further assessed a number of clinical variables--history, risk factors for AD, physical examination--in order to identify predictors for progression of MCI to AD. The only variables useful as predictors were age, the presence of vascular disease, the number of years the individual smoked, the symptom duration and the MMSE score at initial presentation. It was suspected that some of these factors may have been explained by the same variable and a logistic regression analysis was necessary to find out which factors contribute to the prediction. When this was done, the only significant variables remaining were age at onset of memory problems and the MMSE. This predicted progression in about 67% of the MCI group. In addition, retrospectively, individuals who had lack of orientation to time in the MMSE also progressed to AD.

Hippocampal atrophy (MRI volumetrics) may also be useful as a predictor for progression. MCI patients have hippocampal volume that is intermediary between normal individuals and AD patients (who have significant shrinkage). SPECT scanning and APOE genotype did not appear be useful in predicting progression. The researchers set up an algorithm that was a combination of low-tech and high-tech measures--an approach that can be used by physicians in the future. The algorithm allows a physician to establish a score and stratifies the progression of AD in MCI individuals. In the study, individuals that scored zero on the algorithm never progressed to AD and those who scored 4 or more developed AD.

Dr. Petersen, Director of the Mayo Alzheimer's Disease Research Center, gave an update of recent clinical trials on MCI. A definitive diagnosis of AD can only be made after death through the use of neuropathological methods. For the past 15 years, there have been good criteria for probable AD and correspondence between probable AD and definite AD is about 80-90%, if the usual guidelines for diagnosis are used. Research on MCI suggests that there is a transitional point between normal aging and probable AD. The problem for a physician is how to care for a person who presents at this stage and what to tell the family.

The MCI group of patients is an important group to study because they may give us insight into normal aging. From a practical point of view, these individuals may need to be told that they have a cognitive profile that puts them at a greater risk of developing AD, although, as previously mentioned, some patients may not progress to AD. Physicians have to be very careful not to over-diagnose patients with MCI. Do people who fulfil the criteria actually progress to AD at an accelerated rate and, ultimately, can something be done to impede the development of AD in these individuals using cholinesterase inhibitors or secretase inhibitors? Dr. Petersen and colleagues obtained data from the longitudinal study on aging in Rochester, Minnesota. It should be noted that the subjects (largely Caucasian, middle income) were not necessarily representative of the general population. The cognitive function of these subjects has been followed for approximately 20 years. Usually, early in the disease, the patients are not anosagnosic but are actually aware of their memory impairment. MCI patients that meet this criteria progress to probable AD at a rate of 12% per year compared to controls that progress at a rate of about 1-2% per year. According to Dr Petersen, after 10 years, 80% of these patients progress to AD. There are qualitative features that help predict who is more likely to progress to AD and who is not. The inability of persons to benefit from cues, and hippocampal atrophy, were positive predictors of progression.

Currently, clinical trials are underway to test the use of all the second-generation cholinesterase inhibitors in MCI (Table 2) as well as vitamin E, and COX-2 inhibitors. MCI individuals, if well characterized, present a sample population that will progress to AD at a known rate and are an important target group for preventive therapy. Finding a control for this study group is difficult--age-appropriate controls could be contaminated, as they may include subjects who themselves have MCI.

TABLE 2 Clinical Trials in MCI
Sponsor	Duration of Study	Endpoint	Drugs being tested
Alzheimer's Disease Cooperative Study (ADCS)	3 years	Clinical probable AD	Vitamin E Donepezil
Merck Frosst	2-3 years	Clinical probable AD	Rofecoxib
Novartis	2 years	Clinical probable AD	Rivastigimine
Janssen-Ortho	2 years	Clinical probable AD	Galantamine
Pfizer	6 months	Symptomatic improvement	Donepezil

Most individuals with MCI will go on to develop AD. In the future, we may also determine predictive phases of other dementias, where a patient can present with slight impairment in multiple domains, or a slight impairment in a single, non-memory domain. These could be used as predictors of the development and progression of several conditions including Frontotemporal dementia, Lewy body dementia, or even primary progressive aphasia.

At least for the relationship between MCI and AD, we now have available criteria that can allow for clinical trials to determine the efficacy of intervention at this stage, possibly preventing the inevitable progression toward AD.

Dementia: Biological and Clinical Advances--Part I

Dementia: Biological and Clinical Advances--Part II

Further Readings

1. Barber R, Ballard C, McKeith IG, Gholkar A, O'Brien JT, Volumetric study of dementia with Lewy bodies--A comparison with AD and vascular dementia Neurology 2000;54:1304-1309.
2. Chui H. Dementia due to subcortical ischemic vascular disease. Clin Cornerstone 2001;3(4):40-51.
3. Jack CR Jr, Petersen RC, Xu Y, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology. 2000 Aug 22;55(4):484-89.
4. Longstreth WT Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 1996 Aug;27(8):1274-82.
5. McKeith IG, Ballard CG, Perry RH, Ince PG, O'Brien JT, et al. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. 2000 Mar 14;54(5):1050-8.
6. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2001 May 8;56(9):1133-42.
7. Petersen RC. Aging, mild cognitive impairment, and Alzheimer's disease. Neurol Clin. 2000 Nov;18(4):789-806. Review.
8. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Kokmen E, Tangelos EG. Aging, memory, and mild cognitive impairment. Int Psychogeriatr 1997;9 Suppl 1:65-9.
9. Rocca WA, Kokmen E. Frequency and distribution of vascular dementia.Alzheimer Dis Assoc Disord 1999 Oct-Dec;13 Suppl 3:S9-14.
10. Shah S, Tangalos EG, Petersen RC. Mild cognitive impairment. When is it a precursor to Alzheimer's disease? Geriatrics. 2000 Sep;55(9):62, 65-8. Review.

Hannah Hoag, MSc
Contributing Author,
Geriatrics & Aging.

Approximately 8% of Canadians over the age of 65 suffer from some form of dementia. Alzheimer disease accounts for the majority of dementia cases (64%), with vascular dementia the next most common form. This translates to 364,000 Canadians, 65 years of age and older with dementia, and approximately 109,900 new diagnoses this year.¹

The individual suffering from dementia requires a safe physical environment and access to supportive services offering dynamic care that can change with his or her symptoms. Accurately determining the needs of each individual may be difficult for the general practitioner or may be confounded by a clinical environment that the patient may find overwhelming and intimidating. Psychogeriatric home visit services might provide the answer.

In 1980, the Queen Street Mental Health Centre launched the Psychogeriatric Assessment Consultation and Education (PACE) program in Toronto's East-End. A needs assessment of the community and pilot project had previously determined that aging and elderly citizens desired community-based mental health services that would allow them to receive complete assessment, care and follow-up from the comfort of their own homes.

Since then, the Queen Street Mental Health Centre has amalgamated with the Addiction Research Foundation, the Clarke Institute of Psychiatry and The Donwood Institute to form the Centre for Addiction and Mental Health (CAMH).