Alzheimer's: Challenges in the Newly Diagnosed

Alois Alzheimer

Memory loss is a cardinal feature in the presentation and diagnosis of new patients with Alzheimer’s disease(AD).  However, the accompanying neurological and psychiatric problems seen in this population can be significant challenges.  Spalletta and colleagues have recently published a comprehensive assessment of the prevalence and types of problems families and clinicians face. 

Between 2003 and 2005, five Italian outpatient memory clinics studied a series of 1015 patients newly diagnosed with Alzheimer’s disease.  The subjects received a comprehensive assessment that including psychiatric, neurological and behavioral domains.  Men with newly diagnosed AD were contrasted with women newly diagnosed with AD to see if there were any specific gender effects in the findings.   Of interest, despite the new (recent) diagnosis, 40% of men and 47% of women already met criteria for severe dementia.  The authors note that there is significant variability in the timing of presentation for specialty evaluation and assessment.  Some find their way quickly, some only after dementia has progressed to a significant level.

The research team used a structured behavioral inventory called the Neuropsychiatric Inventory (NPI).  A factor analysis of the NPI showed 5 key factors that could be rated as absent, mild or clinically significant.  Here are the factors and prevalence rates in the sample for each of the domains men (women), (*-indicates statistical difference between men and women):

• Psychosis--8% (9%)
• Affective (Depression)--23% (32%)
• Mania- 2% (6%)*
• Psychomotor (agitation/irritability/aberrant motor behavior)—12% (11%)
• Apathy-37% (39%)
• At least one of the five syndromes—56% (61%)

The authors then examined how the prevalence for these neuropsychiatric problems correlated with the severity of dementia.  They found that severity increased four of the problem domains with most severe dementia raising risk from 70% for apathy to raising risk 420% for psychomotor problems.  Of note, depressive symptoms did not increase with severity of dementia. 

The authors note their study highlights the importance of assessing for apathy in this population.  The make it the most prevalent of the neuropsychiatric syndromes in the newly diagnosed with AD.   Apathy has been linked to neuropathological involvement in the medial frontal cortex and the anterior cingulate cortex in AD.

The authors note that their findings support looking for clusters of individual symptoms that make up these key five domains.  It would be helpful for future intervention studies (i.e. pharmacological/behavioral studies) to examine response over these domains.   We are seeing some recent clinical trials break out response of specific behavioral domains for drugs targeting AD.  A recent open label naturalistic study of the drug rivastigmine found apathy measures were more likely to improve than worsen over a 6 to 12 month follow up period.

Wikipedia Commons photo of Dr. Alois Alzheimer, Bavarian physician instrumental in describing the clinical features of dementia and discovering the histological brain changes characteristic of the illness.  Image estimated to be from about 1915 and is in the public domain due to expiration of any copyright.

Spalletta G, Musicco M, Padovani A, Rozzini L, Perri R, Fadda L, Canonico V, Trequattrini A, Pettenati C, Caltagirone C, & Palmer K (2010). Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 18 (11), 1026-35 PMID: 20808086


Gauthier S, Juby A, Dalziel W, Réhel B, Schecter R, & EXPLORE investigators (2010). Effects of rivastigmine on common symptomatology of Alzheimer's disease (EXPLORE). Current medical research and opinion, 26 (5), 1149-60 PMID: 20230208