Frank J. Molnar, MSc, MDCM, FRCPC, Canadian Institutes of Health Research (CIHR) CanDRIVE Research Team, Clinical Epidemiology Program, University of Ottawa Health Research Institute; Division of Geriatric Medicine, Department of Internal Medicine, University of Ottawa; Division of Geriatric Medicine, the Ottawa Hospital; REVTAR Research Group and CT Lamont Centre for Primary Care Research, Élisabeth-Bruyère Research Institute, Ottawa, ON.
Anna M. Byszewski, MD, FRCPC, CIHR CanDRIVE Research Team; Division of Geriatric Medicine, Department of Internal Medicine, University of Ottawa; Division of Geriatric Medicine, the Ottawa Hospital, Ottawa, ON.
Mark Rapoport, MD, FRCPC, CIHR CanDRIVE Research Team; Department of Psychiatry,
University of Toronto; Sunnybrook Health Sciences Centre, Toronto, ON.
William B. Dalziel, MD, FRCPC, Division of Geriatric Medicine, Department of Internal Medicine, University of Ottawa; Division of Geriatric Medicine, the Ottawa Hospital; the Regional Geriatric Program of Eastern Ontario, Ottawa, ON.

There may be up to 1.5 million persons with dementia who are driving in North America. In many jurisdictions, physicians are mandated to assess and report fitness to drive in such patients. Lack of knowledge of patients’ driving status does not protect physicians from lawsuits. There is a paucity of research to aid physicians in the assessment of fitness to drive in persons with dementia. Guidelines recommend the Mini-Mental State Examination, the clock-drawing test, and Trails A and B but lack evidence-based instructions regarding how to interpret such tests. This article provides experience-based approaches to the assessment of fitness to drive in dementia as well as an approach to disclosure of the findings to patients.
Key words: dementia, Alzheimer, driving, family physicians, cognitive testing.

Ekaterina Rogaeva, PhD, Associate Professor, Centre for Research in Neurodegenerative Diseases, University of Toronto, Department of Medicine, Toronto, ON.

There are at least four well-confirmed genes responsible for Alzheimer’s disease (AD), the most common form of dementia. In addition, many reports indicate an association between the disease and genetic variations in different gene candidates. The complexity and interpretation of these studies are discussed using, as an example, the recent discovery of the association between AD and the SORL1 gene. The knowledge obtained from AD genetics is applicable to many other forms of dementia, which are also genetically complex disorders and are almost all associated with the deposition of different aberrant proteins in the brain.
Key words: Alzheimer’s disease, gene, APP, APOE, SORL1.

Antonio Terracciano, PhD, Laboratory of Personality and Cognition, National Institute on Aging (NIA), National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS), Baltimore, MD, USA.
Robert R. McCrae, PhD, Laboratory of Personality and Cognition, NIA, NIH, DHHS, Baltimore, MD, USA.
Paul T. Costa Jr., PhD, Laboratory of Personality and Cognition, NIA, NIH, DHHS, Baltimore, MD, USA.

Individual differences in personality traits are generally stable during adulthood; where there are changes, they are generally in the direction of greater maturity. The trends are similar for men and women and across cultures. With advancing age, people generally become more emotionally stable, agreeable, and conscientious, with better impulse control, but less active and less open to new actions and values than younger individuals. Those trajectories provide several insights into adult development, challenging some negative stereotypes about older adults and serving as a reminder that enduring individual differences are more important than age in understanding personality.
Key words: personality traits, aging, cross-cultural, depression, Alzheimer’s disease.

Ellen Grober, PhD, Department of Neurology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.

We have developed and validated a cost-effective case finding tool for early dementia in primary care that consists of two stages: a rapid dementia screening test administered to all patients over the age of 65 and a second stage to identify memory impairment administered to patients who fail the first stage. The Alzheimer’s Disease Screen for Primary Care (ADS-PC) had high sensitivity and specificity for early dementia and higher sensitivity for AD, and distinguished AD from non-AD dementias. The ADS-PC outperformed the MMSE and worked equally well in African-American and Caucasian primary care patients and in patients that differed in educational level.
Key words: Alzheimer’s disease, early dementia, mass screening, primary health care, neuropsychological tests.

David F. Tang-Wai, MDCM, FRCPC, Assistant Professor, Department of Medicine, University of Toronto; University Health Network Memory Clinic, University of Toronto, Toronto, ON.
Naida L. Graham, PhD, Research Associate, Department of Speech-Language Pathology, University of Toronto; University Health Network Memory Clinic, University of Toronto; Toronto Rehabilitation Institute, Toronto, ON.

Impairment in language is a common finding among individuals with dementia and can be a presenting symptom, particularly in Alzheimer’s dementia and primary progressive aphasia. Early recognition of language dysfunction can help with an accurate diagnosis, management, and prognosis. There are numerous established and validated language evaluation protocols. This article provides a simple means for the primary care physician to identify and evaluate language disorders in dementia, but it is not meant to replace established protocols.
Key words: aphasia, dementia, primary progressive aphasia, semantic dementia, Alzheimer’s disease.

Eran Metzger, MD, Associate Director of Geropsychiatry, Hebrew SeniorLife, Boston; Assistant Professor of Psychiatry, Harvard Medical School, Boston, MA, USA.

The management of depression among individuals with dementia can be one of the more challenging problems in geriatric practice. Depression in dementia is common regardless of the type of dementia and compounds the impairment of the underlying dementing illness. Some symptoms of dementia, including apathy, impaired concentration, and decreased food intake, may be difficult to distinguish from similar symptoms of depression. This article presents background information on the epidemiology and pathophysiology of depression in dementia followed by recommendations for a systematic approach to diagnosis. Treatment modalities including psychotherapy, pharmacotherapy, and electroconvulsive therapy are reviewed.
Key words: dementia, depression, Alzheimer’s disease, psychotherapy, psychopharmacology.

Kristin Casady, MA, Editorial Director, Geriatrics & Aging.

Yes: in the sea of life enisled,
With echoing straits between us thrown.
Dotting the shoreless watery wild,
We mortal millions live alone.
The islands feel the enclasping flow,
And then their endless bounds they know.
–Matthew Arnold

That humans are social creatures who require meaningful interactions with others for happiness is a truism; however, recent research suggests that relating is valuable for more than emotional well-being. Older adults who are persistently lonely, and who perceive themselves as lacking connection and outlets for meaningful interaction, may be more vulnerable to the effects of age-related neuropathology.

A recently published study has linked the development of Alzheimer’s disease with loneliness. The study, published in the Archives of General Psychiatry, has found that lonely people may be at least twice as likely to develop the type of dementia linked to Alzheimer’s disease than individuals who do not report loneliness in advanced age (Arch Gen Psychiatr 2007;64:234-40).

Previous studies have identified a link between social isolation in old age and the risk of cognitive decline and dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. Social isolation refers to connectedness with one’s social environment. Such isolation can be assessed by measuring the extent and quality of social contact and relationships--whether one is married, or has friendships and other social relationships experienced as meaningful, for example. Loneliness is measured more subjectively, and is assessed by asking people about how alone, empty, or abandoned they feel. In other words, the key distinction is between being alone and feeling alone.

In order to test their hypothesis that loneliness may be associated with increased risk of Alzheimer’s disease (AD), researchers conducted a longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. They analyzed 823 older Caucasian persons free of dementia at enrollment who were recruited from seniors’ facilities in the Chicago area. Loneliness was assessed with a 5-item scale at baseline (mean ± SD, 2.3 ± 0.6) and annually thereafter. Participants underwent evaluations including assessments of loneliness, classifications of dementia and Alzheimer’s disease, and testing of thinking, learning, and memory abilities. Loneliness was measured on a scale of one to five, the score increasing with the degree experienced. At death, uniform postmortem brain examinations were conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions.

During the follow-up period 76 of the recruits developed clinically defined Alzheimer’s. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile). Researchers controlled for indicators of social isolation and other covariates, which did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was strongly associated with cognitive decline and development of AD. Of the 90 participants who died and in whom autopsy of the brain was performed, loneliness was not related to pathological findings.
Loneliness was associated with impaired cognitive function at baseline, the authors noted. The basis for the association between loneliness, AD and cognitive decline is not yet known. Their results did not suggest that changes in cognition itself produced behaviours that might create impressions of loneliness, and loneliness did not increase in their study with reported levels of altered cognition. Pathological findings also failed to link amyloid plaques to rates of reported loneliness. In other words, their data do not support the hypothesis that loneliness is a reaction to impaired cognition.

Alternately, the authors offer the possibility that loneliness could compromise neural systems underlying cognition and memory, increasing individuals’ vulnerability to the effects of age-related neuropathology. They propose that neural systems underlying social behaviour may be less varied and elaborate in lonely people and thus less able to compensate for other neural systems under insult from age-related pathology. Given that neither AD pathology nor cerebral infarction could account for the association between loneliness and cognitive decline, they suggest that “novel neurobiological mechanisms” may be involved.
Further findings included data indicating that the association of loneliness and AD-related decline is at least partly independent of depressive symptomatology.
Given these data, the authors concluded that loneliness is a risk factor for, not an early sign of, Alzheimer’s disease. They noted that independent replication of their findings is necessary and would optimally involve longer follow-up and greater diversity of participants.

Weerasak Muangpaisan, MD, FRCPT, Assistant Professor, Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand; visiting fellow, Harris Manchester College, University of Oxford, Oxford, U.K.

Cases of dementia are increasing due to longer life expectancy of the world population. Physicians should be able to recognize common dementia syndromes. After excluding reversible causes of dementia, there are four common dementia syndromes, which are Alzheimer’s disease, vascular dementia, dementia with Lewy body, and frontotemporal dementia. The key points of clinical differences of these dementia syndromes are summarized in this article.
Key words: Alzheimer’s disease, vascular dementia, dementia with Lewy body, frontotemporal dementia, Parkinson’s disease.

Jennifer L. Martin, PhD, Assistant Research Professor, University of California, Los Angeles; Department of Medicine and Research Health Scientist, VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center, Los Angeles, California, USA.

Caregivers often report sleep disturbances in persons with dementia. Older adults with dementia have more nighttime awakenings, less deep sleep, more daytime sleepiness and napping, and experience changing in the timing of sleep. Sleep disorders such as sleep disordered breathing, restless legs syndrome, periodic limb movement disorder, and REM behaviour disorder are more common among individuals with some types of dementia. Sleep problems are associated with difficulties in caregiving and quality of life. As a result, sleep problems should be evaluated and treated. Treatment should always consider nighttime environmental and daytime lifestyle factors.
Key words: sleep, dementia, Alzheimer’s disease, circadian rhythms, sleep disorders.

The accredited CME learning activity based on this article is offered under the auspices of the CE department of the University of Toronto. Participating physicians are entitled to one (1) MAINPRO-M1 credit by completing this program, found online at www.geriatricsandaging.ca/cme

David B. Hogan MD, FACP, FRCPC, Professor and Brenda Strafford Chair in Geriatric Medicine, University of Calgary, Calgary, AB.

A number of agents are available for treatment of Alzheimer’s disease (AD). They include drugs with a specific indication for AD, nutritional supplements, herbal preparations, and drugs approved for other conditions. Cholinesterase inhibitors (ChEIs) such as donepezil, galantamine, and rivastigmine are modestly effective for mild to moderate stages of AD. Memantine has a slight, beneficial effect on moderate to severe stages of AD. As ChEIs and memantine have different mechanisms of action, they can be used together. Antioxidants, B vitamins, anti-inflammatories, HMG-CoA reductase enzyme inhibitors, and sex steroids can not be recommended for the treatment of AD at the present time.
Key words: Alzheimer’s disease, drug therapy, cholinesterase inhibitors, memantine, dementia.