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Phenotype of depression in Alzheimer's disease (AD) with APOE genotype
Abstracts
Alzheimer's disease (AD) was measured using the Computcrizet.! Neuropsychological Test Ballery (CNTS) and the All.heimcr's Disease Assessment Scale-Cognilivc Subscnlc (ADAS·Cog) in this .7-center, double-blind. placebo-controlled study. After :l two-week I~d-in, 343 pnticlllS (appro"imalely 85 per panel) were randomly assign.:d to receive 25mg, 50mg or 75mg xnnometine tanrate or placebo three limes daily for 24 weeks. followed by :l 4-weck single-blind placebo washout period. Cognitive function WllS assessed ot randomization and nf:er 4, 8, 12, 24. and 28 weeks. Endp-oint analysis using the last ob~ervation plior to discontinuation revealed a dose-response effcct on the CNTB summary score which was statistically significllnt when the analysis wa'i based on the numerical score (p;;:O.044) but was a trend (p=O.066) based on analysis of ranked data. Pairwise comparisons of the treatment nnns favored 75mg tid over placebo (adjusted mean treatment difference 2.77 points; p=O.039. row; p=O.066. ranked). Significant treatment effects Wl:CC also seen on three of the CNTB modules, including improved simple reaction time (p=O.032). The CNTB was highly correlated with the ADAS.cog (rt).74; p
546. PHENOTYPE OF DEPRESSION IN ALZHEIMER'S DISEASE (AD) WITH APOE
mOL PSYCUlATRY 1996:39:5110-666
661
547. BASAL GANGLIA MORPHOLOGY IN GERIATRIC MANIA J.P. Bocksbergerl,Z, R.C_ Young l , B. Kalayam l , C. Elkin t •3 , & Alexopoulos t
a.s.
IThc New York Hospital - Cornell Medical Center. Wes~chcslcr Division. White Plains. NY: ~Univcrsity of Geneva, Geneva, Switzerlanu; JWhile Plains HospiUlI. White Plains, NY
Abnonnal brain morphology ha.~ been reponed in young 3dult and geriatric manic p:llients. Decreased volume of ba.~al ganglia nuclei h:tS been noted in m:ljor dcprt:ssives. We therefore ex.amined ctlUllalc and putamen volumes in gerialric manic patients and controls; wc hypothe. sized smaller volumes in the JXltient group. Psychi:llric inp:uicnts aged 60 ye:lrs or older with manic disorder by RDC (n= 23) and same llge nomml controls (n= 13) wen: stUdied. Intcmlcdiatc T2 - weighted axial image!> were obtained using II I.S Tesla magnetic rcson3nce system. Volumes of caUdll[C and putamen nuclei and cerebral hemispheres were determined by a system3tic sampling stcreologic method. Volumes or right and left caudale and putnmen, corrected for cercbrnl hemisphere volumes. wen: each smaller in patients than in controls (p
GENOTYPE M. Cantillon, W. Barker, D. Harwood. M. Mullan, & R. Duara Wien Center, Mt. Sinai Medical Centcr. Minmi Bench, A.. The purpose of this study was to detennine whelher there is n significant relationship between Ihe APOE genotype and AD depression, fn 149 AD patients with lit least one ApoE E4 allele (E4+) and 138 AD patients without an ApoE E4 IllIelll (E4-), we compared demographic (age of onsct. cducution, gender) cognitive impainncnt (Folstein) lind psychiatric features (Hamilton score. percent with ull depressive diagnoses, percent with m:ljor depression alone rmd percent Wilh wle vs early onset depression). For u subset of 126 AD subjects. the Comell depression scale was measured. A SeparJle sample of 60 cognitivcly normal elderly subjects was also evaluated for depression. Age-nt-onsct was 73~7 yrs in the E4+. 76±8 yrs in lhe E4- subjects (p:::O.OOO4). Hamilton scores were signlficantl)' higher in the E4· subjects (E4-:8.0±4.3 vs E4+ :9.4±6.2: p=O.04). No signilicant differences were secn on Cornell depression total scale scores, However, scores on the Cornell behavior index were higher in the E4- subjects (E4-: t.3± 1.2 vs E4+:0.8± 1.0: p= 0.004). Funher. e4- subjects presented with significantly incrcased levels of psychomotor rctanlntion (E4-:38% vs E4+:16%: p=O.OO7). There were no dJfferences in years of eduCDtion and gcnd~r (68% female for E4+ v!o 65% for e4.) between the two groups. Overall, no significant differences in diagnosis of depression Were evident. However. there was 11 trentJ for the depression to be of late onset type in the 54+ patients (E4+: 35% vs E4·:11%: p=O.05). In Ihe nonnaillample. there were no diffcrences in Hamillon scores or diagnoses of depression in E4+ vs E4- subjecls. Unlike a report by Krishnan et :II (1994) we fount.! no e4+ relation...hip to late onset depression in cognilivcly norm:11 SUbjects. As we reported in a smuller group (Cantilion el nl 1995), behavioml symptoms of depression in AD may be less common in e4+ subjects.
548. CIRCADIAN REST-ACTIVITY RHYTHMS
IN DEMENTED NONDEMENTED ELDERS AND THEIR CAREGIVERS C.P. Pollak2 , P.E. Stokesl , & P.R. MouriJhe l IThe New York Hospitlll.Comell Me~ical Cenler, White Plains, NY 10605: znlC Ohio State Univcl'!iily·Univcrsity Medical Cenrer, Columbus. OH Disruptive nocturnal behavlon; of elderly people often threaten thl: caregiving mrangcmenls on which their community tenure dCpt:nus. Demenl!ng disorders arc especially prone to result in disrupted sleep anti agitated behaviors ("sundowning"). Circadian rest-activity cycles were therefore compared in community residenls consisting of demented ciders :lnd their caregivcr.; as well as nondemented elders and their caregivers. Activity was measured and stored with wrist-worn micro processor record(!rs. A novel methOl..1 wa.~ devised 10 detect periods when the rceorders had not beell worn. Such non-compliance anif.,ct was surprisingly common. If not removed, it would have biased the llclivity Icvel datll toward small values normally as~oci:lled with sleep. Mean houri)' aClivity pallems showed that demen leU nnd nondementcd elders were more IIcti\'e lit night than their caregivers and presumably slept less soundly. However, demented subjects were contrastingl)' less active in the daytime than their nonclcmenle,", peers as well as their caregivers. The consequent l1aller rest-activity rhythms of the demented elders nre not entirely explained by Ilge, nor by decC'Cllsed output of OJ circadian p:lcem~ker. According to filled cosine models. lhe phase of the circadian rest-activity cycle recorded peaked between 2-3 PM in aU elder and caregiver groups llnd did not significantly differ among them. The increased activity of elders at night i~ probably explained by sleep disorders which remain to be identified.
Alzheimer's disease (AD) was measured using the Computcrizet.! Neuropsychological Test Ballery (CNTS) and the All.heimcr's Disease Assessment Scale-Cognilivc Subscnlc (ADAS·Cog) in this .7-center, double-blind. placebo-controlled study. After :l two-week I~d-in, 343 pnticlllS (appro"imalely 85 per panel) were randomly assign.:d to receive 25mg, 50mg or 75mg xnnometine tanrate or placebo three limes daily for 24 weeks. followed by :l 4-weck single-blind placebo washout period. Cognitive function WllS assessed ot randomization and nf:er 4, 8, 12, 24. and 28 weeks. Endp-oint analysis using the last ob~ervation plior to discontinuation revealed a dose-response effcct on the CNTB summary score which was statistically significllnt when the analysis wa'i based on the numerical score (p;;:O.044) but was a trend (p=O.066) based on analysis of ranked data. Pairwise comparisons of the treatment nnns favored 75mg tid over placebo (adjusted mean treatment difference 2.77 points; p=O.039. row; p=O.066. ranked). Significant treatment effects Wl:CC also seen on three of the CNTB modules, including improved simple reaction time (p=O.032). The CNTB was highly correlated with the ADAS.cog (rt).74; p
546. PHENOTYPE OF DEPRESSION IN ALZHEIMER'S DISEASE (AD) WITH APOE
mOL PSYCUlATRY 1996:39:5110-666
661
547. BASAL GANGLIA MORPHOLOGY IN GERIATRIC MANIA J.P. Bocksbergerl,Z, R.C_ Young l , B. Kalayam l , C. Elkin t •3 , & Alexopoulos t
a.s.
IThc New York Hospital - Cornell Medical Center. Wes~chcslcr Division. White Plains. NY: ~Univcrsity of Geneva, Geneva, Switzerlanu; JWhile Plains HospiUlI. White Plains, NY
Abnonnal brain morphology ha.~ been reponed in young 3dult and geriatric manic p:llients. Decreased volume of ba.~al ganglia nuclei h:tS been noted in m:ljor dcprt:ssives. We therefore ex.amined ctlUllalc and putamen volumes in gerialric manic patients and controls; wc hypothe. sized smaller volumes in the JXltient group. Psychi:llric inp:uicnts aged 60 ye:lrs or older with manic disorder by RDC (n= 23) and same llge nomml controls (n= 13) wen: stUdied. Intcmlcdiatc T2 - weighted axial image!> were obtained using II I.S Tesla magnetic rcson3nce system. Volumes of caUdll[C and putamen nuclei and cerebral hemispheres were determined by a system3tic sampling stcreologic method. Volumes or right and left caudale and putnmen, corrected for cercbrnl hemisphere volumes. wen: each smaller in patients than in controls (p
GENOTYPE M. Cantillon, W. Barker, D. Harwood. M. Mullan, & R. Duara Wien Center, Mt. Sinai Medical Centcr. Minmi Bench, A.. The purpose of this study was to detennine whelher there is n significant relationship between Ihe APOE genotype and AD depression, fn 149 AD patients with lit least one ApoE E4 allele (E4+) and 138 AD patients without an ApoE E4 IllIelll (E4-), we compared demographic (age of onsct. cducution, gender) cognitive impainncnt (Folstein) lind psychiatric features (Hamilton score. percent with ull depressive diagnoses, percent with m:ljor depression alone rmd percent Wilh wle vs early onset depression). For u subset of 126 AD subjects. the Comell depression scale was measured. A SeparJle sample of 60 cognitivcly normal elderly subjects was also evaluated for depression. Age-nt-onsct was 73~7 yrs in the E4+. 76±8 yrs in lhe E4- subjects (p:::O.OOO4). Hamilton scores were signlficantl)' higher in the E4· subjects (E4-:8.0±4.3 vs E4+ :9.4±6.2: p=O.04). No signilicant differences were secn on Cornell depression total scale scores, However, scores on the Cornell behavior index were higher in the E4- subjects (E4-: t.3± 1.2 vs E4+:0.8± 1.0: p= 0.004). Funher. e4- subjects presented with significantly incrcased levels of psychomotor rctanlntion (E4-:38% vs E4+:16%: p=O.OO7). There were no dJfferences in years of eduCDtion and gcnd~r (68% female for E4+ v!o 65% for e4.) between the two groups. Overall, no significant differences in diagnosis of depression Were evident. However. there was 11 trentJ for the depression to be of late onset type in the 54+ patients (E4+: 35% vs E4·:11%: p=O.05). In Ihe nonnaillample. there were no diffcrences in Hamillon scores or diagnoses of depression in E4+ vs E4- subjecls. Unlike a report by Krishnan et :II (1994) we fount.! no e4+ relation...hip to late onset depression in cognilivcly norm:11 SUbjects. As we reported in a smuller group (Cantilion el nl 1995), behavioml symptoms of depression in AD may be less common in e4+ subjects.
548. CIRCADIAN REST-ACTIVITY RHYTHMS
IN DEMENTED NONDEMENTED ELDERS AND THEIR CAREGIVERS C.P. Pollak2 , P.E. Stokesl , & P.R. MouriJhe l IThe New York Hospitlll.Comell Me~ical Cenler, White Plains, NY 10605: znlC Ohio State Univcl'!iily·Univcrsity Medical Cenrer, Columbus. OH Disruptive nocturnal behavlon; of elderly people often threaten thl: caregiving mrangcmenls on which their community tenure dCpt:nus. Demenl!ng disorders arc especially prone to result in disrupted sleep anti agitated behaviors ("sundowning"). Circadian rest-activity cycles were therefore compared in community residenls consisting of demented ciders :lnd their caregivcr.; as well as nondemented elders and their caregivers. Activity was measured and stored with wrist-worn micro processor record(!rs. A novel methOl..1 wa.~ devised 10 detect periods when the rceorders had not beell worn. Such non-compliance anif.,ct was surprisingly common. If not removed, it would have biased the llclivity Icvel datll toward small values normally as~oci:lled with sleep. Mean houri)' aClivity pallems showed that demen leU nnd nondementcd elders were more IIcti\'e lit night than their caregivers and presumably slept less soundly. However, demented subjects were contrastingl)' less active in the daytime than their nonclcmenle,", peers as well as their caregivers. The consequent l1aller rest-activity rhythms of the demented elders nre not entirely explained by Ilge, nor by decC'Cllsed output of OJ circadian p:lcem~ker. According to filled cosine models. lhe phase of the circadian rest-activity cycle recorded peaked between 2-3 PM in aU elder and caregiver groups llnd did not significantly differ among them. The increased activity of elders at night i~ probably explained by sleep disorders which remain to be identified.